Therapeutics

第四届中美纳米医学与纳米生物技术年会

The 4th Annual Meeting of Chinese American Society of Nanomedicine and Nanobiotechnology

会议手册 Conference Handbook

19th - 22nd August 2019 | Hangzhou, China Welcome Message

Dear Friends and Colleagues, On behalf of the organizing committee and Zhejiang University, the hosting institution, we welcome you to Hangzhou for the 4th International Symposium for Chinese American Society of Nanomedicine and Nanobiotechnology (CASNN) during August 20-22, 2019. CASNN was initially proposed by a group of active Chinese scholars in USA and China as an informal WeChat group and formally established in 2016. Its primary objective is to promote international communication, primarily between USA and China, for the advancement of nanomedicine and nanobiotechnology and to foster inclusive and collaborative interactions among researchers and institutions working in those areas. This annual symposium series has been successfully held in Nanjing (2018), Suzhou (2017) and Beijing (2016). The 4th CASNN meeting committee has invited and assembled a strong list of international speakers from academia, industry, and government agencies. This list includes 130 prominent scientists and leading experts with diverse backgrounds in Engineering, Chemistry, Medicine, and Pharmacy. In addition, there are more than 300 poster presentations contributed by graduate students, postdoctoral and medical researchers. In the past twenty years, nanomedicine and bionanotechnology have experienced remarkable advances enabled by scientific discoveries and breakthroughs. We felt that it is imperative to reiterate the significance of fundamental and transformative concepts. Thus, we place the conference theme under “Transform Nanomedicine with Breakthrough Thinking”. The meeting also includes discussion forums for Emerging Leaders and Rising Stars, aiming to stimulate provocative discussions on the most critical issues in nanomedicine and nanobiotechnology. We thank the staff members, volunteers, and session chairs for helping us build this exciting program. The organizing and scientific committees will make every effort to make sure your participation is scientifically rewarding, and your trip to Hangzhou (the Paradise on Earth) pleasurable and relaxing. Yours Sincerely,

Co-Chair: Youqing Shen Co-Chair: Honggang Cui Ph.D., Professor Ph.D., Associate Professor Center for BioNanoEngineering Dept. of Chemical and Biomolecular College of Chemical and Biological Engineering Engineering Institute for NanoBioTechnology Zhejiang University, 38 Zheda ST The Johns Hopkins University Hangzhou, China 310027 3400 N. Charles Street, Baltimore, MD 21218 Phone/Fax: 86-571-87953993 Phone: 001(410) 516-6878 E-mail: [email protected] E-mail: [email protected]; http://orcid.org/0000-0003-1837-7976 http://www.jhu.edu/cui

1 欢迎辞

第四届中美纳米医学与纳米生物技术年会由中美纳米药物与纳米生物技术学会（CASNN）

主办，前三届的会议（2016，北京；2017，苏州；2018，南京）取得了巨大的成功。

第四届大会会议的主题是“推动纳米医学发展的变革性思维——Transform

Nanomedicine with Breakthrough Thinking”，旨在共同探讨纳米药物/纳米医学的发展愿

景、面临的挑战及解决策略，推动纳米医学与纳米生物技术相关产业的蓬勃发展, 促进中美

纳米医学与纳米生物技术领域项目和技术的交流、合作。

会议议题

※变革性纳米药物论坛

※先进纳米药物/制剂与功能辅料

※肿瘤免疫治疗的纳米药物/制剂

※用于疾病检测的生物传感器和生物芯片

※纳米药物的个性化治疗和临床转化

会议已邀请来自中国、美国、加拿大、日本、韩国、新加坡等国家和地区的院士和专家

及国内知名药企人员，预计参会人数约 500 人。会议将于 2019 年 8 月 19 号报到，20-22 日

在杭州举行。

我们热忱欢迎大家出席此次学术盛会！期待在各位同行的支持下，本次会议将取得圆满

成功！

大会主席

申有青教授崔宏刚教授

浙江大学约翰霍普金斯大学

申有青教授崔宏刚教授

浙江大学约翰霍普金斯大学

2 主办单位中美纳米医学与纳米生物技术学会（CASNN）

承办单位浙江大学杭州市萧山区人民政府

协办单位萧山区委人才办浙江大学生物质化工教育部重点实室萧山区投资促进局冷泉港生物科技股份有限公司萧山科技城管理局浙江省药学会生物制药专业委员会化学工程国家重点实验室（浙江大学）浙江湘湖影视文化有限公司浙江理工大学浙江原始资本管理有限公司

学术委员会主任：陈小元美国国立卫生研究院程建军伊利诺伊大学蒋兴宇中国国家纳米科学中心成员: 蔡林涛中科院深圳先进技术研究院李春 MD 安德森癌症中心蔡伟波威斯康星大学麦迪逊分校刘滨新加坡国立大学陈小元美国国立卫生研究院刘庄苏州大学程建军伊利诺伊大学申有青浙江大学崔宏刚约翰霍普金斯大学王均华南理工大学高明远中国科学院化学研究所王强斌中科院苏州纳米所高虓虎华盛顿大学张灿中国药科大学宫绍琴威斯康星大学麦迪逊分校张良方加州大学圣地亚哥分校顾臻加州大学洛杉矶分校

3 Opening and Plenary Conference Hall Opening Ceremony •Welcome Speech from Lizhong Wang, Vice President of Zhejiang University Chairs: •Welcome Speech from Xiaoshan District 08:30-09:00 •Introduction of Xiaoshan Investment Policy Youqing Shen •Introduction of Xiaoshan Science and Technology Polis •Unveiling of CASNN-Xiaoshan Center for Technology Translations Prof. Yuliang Zhao 09:00-9:30 National Center for Nanoscience and Technology CASNN Honggang Mechanisms of Nanotoxicity and Nanomedicine Cui Prof. Shuming Nie Award Youqing Lectures University of Illinois at Urbana-Champaign 9:30-10:00 Nanotechnology: from Single Molecule Raman Spectroscopy to Shen Image-Guided Cancer Surgery Opening Prof. Nicholas A. Peppas 20 Morning 20 Morning 10:00-10:40 Plenary University of Texas at Austin Yuliang Zhao Lecture Molecular Recognition at the Nanoscale Level 10:40-11:00 Coffee Break & Photographing

August Prof. Paul S. Weiss University of California, Los Angeles 11:00-11:30 Adding the Chemical Dimension to Lithography at All Scales: Enabling Cellular Therapies & Other Adventures in Biology and Medicine Jianjun 11:30-12:00 Plenary Prof. Justin Hanes Cheng Lectures Johns Hopkins University Sarah Gong Nanomedicine: From Concept to Success in the Clinic 12:00-12:30 Prof. Kinam Park Purdue University PLGA Formulations: Understanding the Complexity of the PLGA Assay Lunch August 20 Afternoon 16:30 16:00- 15:30- 15:00- 14:30- 14:00- 13:30- - 16:40 16:30 16:00 15:30 15:00 14:30 14:00 Lectures Plenary Plenary Dynamic Molecular Fluorescent Probeswith Assembling Nanoparticles TargetingTumor Microenvironment for Biomedical Engineering for ImprovingHuman Health Enabling Platform for Transforming Platform Enabling Developing and How to Get Published in High Impact Journals, Journals, Impact High in Published Get to How Editor East China University of Science & & Technology Science of University EastChina Perspectives of the Publisher the the Editor and of Perspectives University of North Carolina at Chapel Hill at Chapel Carolina of North University Shanghai Selection Bioscience Ltd. Co. Bioscience Selection Shanghai - in Supramolecular Phototherapy - Prof. Chief, NatureBiomedical Engineering Executive Publisher,Elsevier Dr. Fernanda Kinam Prof. Huang Leaf Dr. Dr. Immunotherapy Nanomedicines Dr. Jilin University Prof. Xi Zhang Coffee Prof.He Tian Fuyao Pep Pep Park, EIC of JCR Park, of EIC Pàmies Break Zhang Ogochi Youqing Xingyu Xiaohu Can Zhang Can Chairs: Jiang Gao Shen August 20 Afternoon 18:00- 17:40- 17:20- 17:00- 19:00- 16:40- 19:00 18:00 17:40 17:20 21:30 17:00 Peptide Nanofibers Enzyme University Brandeis Bing Xu Polymers BiopharmaceuticalsBrush with MakingOligonucleotides Better University Northeastern Ke Diagnosis Early and UltrasensitiveAfterglow Imaging OpticalReportersMolecular for TechnologicalNanyang University Kanyi From Fundamentals to Applications Nanomedicines: Clearable Renal University ofTexasat Dallas Jie Session Zhang Zheng Pu Chairs: Chairs: (Conference Hall A) Hall (Conference - Instructed Self I: New I: Xintao Xinyuan Frontiers Shuai - Assembly of Zhu Dinner (GrandCentury New Hotel) Nanomedicines TraffickingCellular and Peking Qiang Bioadhesive BiodegradableNanoparticles Enhancing University ofTexas at Yi University State Penn Yong Self Aix Ling Dendrimersfor BiomedicalApplications of LiveCells In Situ Nanomanufacturing on the Surface Hong - - Marseille University Session Assembling Supramolecular Supramolecular Assembling Peng Poster Award SelectionPoster Award Wang Zhang University Chairs: Yi Chairs: (Conference Hall B) Hall (Conference Poster Exhibition Strength II: Yong Wang Yong Therapeutics I Therapeutics Hong Arlington Bioresponse of of Chromosome 17P Loss 17P Chromosome Negative Breast Cancer with Precision Medicinefor Treating Triple University Indiana Xiongbin Selective Membrane Destruction Membrane Selective Phenylboronate High Gene Technology & Univ. China Science of of Yezi Shanghai Shanghai Yongzhuo birds and Macrophage Targeting Tumor Nanomedicine Unimolecular Vehicle for Molecular Bottlebrush as an Sun Yongming Chairs: Chairs: Session Yat You - One - Sen University (Conference Room) (Conference Lu Instit - Yezi Yongming - Huang Chen stone" TherapeuticStrategy Transfection EfficacyUsing III: Therapeutics II Therapeutics III: . of Materia Materia of . You - MicellesHighly with Associated Metablism Chen Medica as “Two as , CAS - August 21 Morning 09:50- 09:35- 09:20- 09:00- 08:40- 08:20- 08:00- 10:00 09:50 09:35 09:20 09:00 08:40 08:20 Nanomedicine RolesProtein theof Corona in Technology and Nanoscience for Center National Chunying Immunotherapy Nanoparticles for Cancer Stimuli CAS Shanghai Haijun Bio Technology & Univ. China Science of of Yucai Small Hepatic Metastatic Nodules Nanomedicine: Less is More? is Less Nanomedicine: MultifunctionalityClinical in Centre Cancer Margaret University ofToronto Gang Replacement Therapies Replacement Applications for Type 1Diabetes Cell Toroidal Microgels and Their Cornell Minglin Devices Delivery Glucose University ofCalifornia, Zhen Session - Interfaces of NanoparticlesInterfaces with of Gu Zheng Wang Chairs: Chairs: - Yu University (Conference Hall A) Hall (Conference Activatable Prodrug - Ma Responsiveand Insulin Instit Chen I: New I: Minglin Chunying . of Materia Medica Materia of & Princess Ma Frontiers Los Angeles Chen , PotencyCancer Vaccine of Lymph Node Targeting for Improved University Sichuan Xun Immunotherapy Selenium MedicinalChemistry and Cancer Jinan University Tianfeng Performance of Liposomes of Performance KeyRegulating Proteins Plasma Fudan University Changyou Immunotherapy Situ in with AntitumorEnhanced Activity of Specific Immune Tolerance Immune Specific NanomaterialsAntigen for- Inducing Drexel Hao Cheng Materia of Institute Shanghai Yaping Vaccinations ResponsesImmune Enhanced for SystemicGastrointestinalBridging and CAS Engineering, Institute of Process Guanghui Session Sun University Li Chen (Conference Hall B) Hall (Conference Ma Zhan I Chairs: Chairs: Coffee Break Coffee I: Hao Immunot Cheng Xun Sun Nanovaccines Medica herapy in vivo in Icb , CAS CascadeAntitumor Therapy Nanogels Regulatable AssemblyBioactivity and EnzymeInstructed Self PeptideFolding, Nankai University Zhimou Phototheranostics Complexation: SupramolecularA Tumor Nankai University Dong Tongji Qigang Nerves in Living Mice/Rats Living in Nerves the Lymphatics,of Imaging Adipose, and Multi Shanghai Liqin Cancer Cancer of HybridEngineering University Fudan Zhihong Humans for Fluorescence TransistorStrategypH a Using Nanoprobe TargetingAcidosisCancer: in A New UT Southwestern Medical Center Baran Session sheng Xiong - Functional PolymerFunctional Dots for University D. Sumer - Responsive Host Responsive Theranostics Wang Yang Yang Nie (Conference Room) (Conference Jiao Tong University for for Chairs: Chairs: Guo Biocatalysis Photothermal Zhihong III: Diagnostics - Guided Surgery in Zhimou Strategy Nanovesicles Nie - Guest of Enzymeof Yang - Biological - Laden Laden for for - August 21 Morning - 12:30 - 12:05 - 11:50 - 11:35 - 11:20 - 11:00 - 10:40 - 10:20 - 10:00 13:30 12:20 12:05 11:50 11:35 11:20 11:00 10:40 10:20 Therapy PolypeptideNanomaterials for Cancer Changchun Jianxun OxidaseGlucose Shenzhen University HealthScience Center Peng Huang Disrupting Agents Vascular of Targeting Vessel Tumor PolymericImproves Conjugation the of Instit. Changchun Zhaohui Cancer Phototherapy NanoparticlesBODIPYBifunctional for University Soochow Huabing Chen - Selenium Self Tsing Huaping Removal and Delivery Active for Cloaking Membrane Nanomachines University ofCalifornia,San Diego Liangfang Applications Zwitterionic Materials forNanomedicine Washington of University Shaoyi Hai through Kinetically Controlled Assembly NPs Complex Polyelectrolyte Engineering Johns HopkinsUniversity Session - - Chairs: Chairs: AssemblyAnticancer andActivity of Quan h ua University Jiang Ding Tang Xu Containing Compounds (Conference Hall A) Hall (Conference Zhang Zhang Mao Instit Huaping I: New I: Biointerfacing . of AppliedChemistry, CAS - Based Cancer Therapy Cancer Based Applied Xu, Xu, Haiquan Frontiers Chemistry via Cell Mao , CAS University of Washington of University Xiaohu Imaging and Therapy and Imaging Tagging Therapeutic Applications MALDI Hsing Biodistributionof NP - Sequence Univ. 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Photoaccustic Nanomimics - R tumors R tumors and August 21 Afternoon 13:30- 16:20- 16:05- 15:50- 15:30- 15:10- 14:50- 14:30- 14:10- 13:50- 13:50 16:30 16:20 16:05 15:50 15:30 15:10 14:50 14:30 14:10 RegulatingMolecularfor Biomedical Motion Applications University Nankai Dan Ding Multimodal Cancer Therapy Supramolecular Interaction Based Polymeric Nanomedicine for University Zhejiang Zhengwei Resistance Drug Cancer for Overcoming Nanoparticle Responsive Cold Park College Maryland, of University Xiaoming Paper Cranfield University Zhugen Immunotherapy ( Matrices Polymer Liquid University ofMinnesota TwinCities Chun Wang Peamotecan Virginia CommonwealthUniversity Hu EngineeringEndothelial Leakiness Nanoparticles with Singapore of University National Leong Tai David Therapies Application of Nanotechnologies for Enhanced Stem Cell University State Carolina North Ke Editing Machineries Non University ofWisconsin Shaoqin Nanopolymer Cheng Yang - Viral - Origami DeviceEnablingLow Yang Sarah Gong Sarah Gong He Nanoplatforms Mao , a Novel Chronotherapeutic Session Chairs: for Brain Cancer Brain for (Conference Hall A) Hall (Conference Xiaoming - Madison I: New I: LPMs for the Delivery of CRISPR Genome Genome CRISPR of Delivery for the ) for Delivering Cancer Cancer for ) Delivering He, He, Zhugen Frontiers - Cost and Rapid Diagnosis Yang Coffee Break Coffee Bionanotechnology Pharmaceutical of Problems Challenge The Minjiang Lee Living University Pharmaceutical China Can Advances Tumorin TargetingStrategies of Nanomedicine Huazhong Xiangliang Modulate the Osteogenesis MicroenvironmentBiodegradableof the Implants pH can Technology, Advanced of Institutes Shenzhen Haobo Delivery Systems Delivery Versatile Organic/InorganicNanohybrids as Multifunctional Myocardial Infarction Rabbitin Models NanoparticlesAlbumin Precisionof Acutefor Imaging MR University Sichuan Mi Peng Beijing University of Chemical Technology Technology Chemical of University Beijing Nana BioinspiredChiral Supramolecular Hydrogels Tong Jiao Shanghai University Chuanliang Zwitterionic PolymerSurfactants forDelivery Drug Wayne University State Zhiqiang Constructing Chiral Probes forBioimaging Biosensingand Jiangnan Chuanlai Jia Zhang Zhao Cyto Pan Cao University University Xu University of Science and Technology and Science of University Chairs: - Yang Pharmaceuticals for Tumor TherapyPharmaceuticalsTumor for Feng Session Chuanliang (Conference Hall B) Hall (Conference II: Therapeutics both Feng, Feng, in vitroin Zhiqiang and CAS Cao in vivo in August 21 Afternoon 14:30- 14:15- 14:00- 13:45- 13:30- 16:15- 16:00- 15:45- 15:30- 15:15- 15:00- 14:45- 14:45 14:30 14:15 14:00 13:45 16:30 16:15 16:00 15:45 15:30 15:15 15:00 Bionic Artificial Virus Delivers CRISPR/Cas9 Genome Editing System for Cancer Therapy Sichuan Changyang - Genome Therapeutic of Delivery University Zhejiang Yuan Ping BiodegradableNanoparticles for CRISPR/Cas9 Genome Editing Delivery CAS Chemistry, Institute of Wang Ming BiologicalEffects of Environmental Nanoparticles and Technology Center Nanoscience for National Ying pH Nankai University Shutao Targeting Materia of Institute Shanghai Pengcheng Magneto University Southeast Fang a “Don’t with Delivery Drug to System Barrier Reticuloendothelial the Overcoming (China) University Southwest Chong Li The Application of NanomedicineProdrug Anticancer in Therapy Technology Chemical of University Beijing Qingsong Self Natural of Engineering Reverse Minjiang Vladimir L. 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Cell Soochow University Chao Changchun Wantong Cancer Nanotechnology Institute of ProcessEngineering, CAS Niu Chairs: Chairs: BasedNanoparticles for Targeted Jiaotong Xia Wang University Liu Yong Li Therapy - Jiao Tong Pemetrexed Univ.of Science and Technology Song Peptide Assemblies with Tunable - Instit (Conference Hall A) Hall (Conference Induced EmissionMaterials with - Harvesting Strategy Jinyao University - Based Nanoparticles for Efficient . of Applied Chemistry, CAS Targeting University Assemblies Combine Cancer Cancer Combine Assemblies Liu, Liu, Microbiome Wantong Song for BanquetPresenting and Awards Nanomedicine Rising Star Forum NanomedicineStar Rising Fudan Xiaomin NIR Fluorescence Guided Drug Delivery Chengchao PharmaceuticalChina University Xue PharmaceuticalChina University Zhanwei Cancer Cancer Multifunctional Metal Xiamen University Nanozymes Hybrid Biomimetic TumorGuided Photothermal ATPMRI Deep Penetrationthe and for Promoting Extracellular by Fueled Nanoclusters Switchable Size Applications Biomedical for Assemblies Nanoparticle Oxide Iron Multifunctional Zhejiang University Qiyue for Tumor AIEProbe Conjugated Theranostic Sichuan University Gaocan Accelerated O PhotodynamicTherapy against Hypoxic Tumors Shanghai Jiao Tong University Zixiu University of Macau Yunlu Mcro PreparationBiomedical and Applicationof Changchun Maolin Herceptin Nanoparticles Coordination Based Gadolinium Hemoglobin by Radiotherapy In Vivo Polymers/Frameworks torial Worm Yang Chairs: Du / Treatment of HER2- Treatment - Wang University Dai Dai Nano like Nanocrystal Micelles for the for Micelles Nanocrystal like Multimodal Imaging and Enhanced Cancer Cancer Enhanced and Imaging Multimodal Theranostics Li Pang Li Zhou - Conjugated Paclitaxel LoadedPaclitaxel PCL Conjugated Bioimaging (Conference Hall B) Hall (Conference 2 Chu Instit Generation for Enhanced Starvation and Covalent Organic Xiaomin . of Applied Chemistry, CAS - and Accurate Drug Delivery OrganicNanostructure for Positive Breast Cancer Breast Positive with Self with Li, Therapy - Encapsulated Encapsulated Maolin - Supplied H Nanoparticles Combina Pang - + PEG PEG and - Shape Copolymer Tumor Acidityand Oxidation Univ.of Science Technology & of China Zhishen Photo Graphene Univ.Electronic Science & of Chunhui Microenvironment with Sizeand Charge Transformability in Tumor Hyaluronan Instit Zhaoqing Membrane Inhibitionof Pathogen Adhesion by Bacterial Outer Wenzhou Medical University Yijie /Paclitaxel Nanoparticles Preparation and Characterization of Weifang Medical University Xiaoming Nanocarriers Ionic FunctionalPolyester and Their Application as Institute of Chemistry, CAS Liuchun Zheng Delivery Drug Targeting “Self Soochow University Han Liang SynergisticAntineoplastic Effects of Anti Beijing Institute of Technology Yuanyu siRNA and ROSand siRNA Carriers Transmembrane siRNA Deliveryby Small Chemical Wuhan University Wanyi Chen . of of . - Chairs: - Promoted”Nanoparticles for Brain Metastasis - Immunotherapy Boosted DrugBoosted DeliveryEfficacy Tai Ge Materia Huang Wu Cong Cui Based Hybrid - Prodrug Coated Nanoparticles Coated (Conference Room) (Conference for Anti for Zhishen - Responsive Polymeric Nanomicelles Media, Peptide Filomicelles - Tumor Drugs Nanotheranostics CAMS Ge Technolgy Nanoparticle Clusters , - Responsive Block Yuanyu for Nanoparticle Quercetin of China of Huang - RRM2 for Cancer Conference Hall Prof. Weihong Tan Chairs: 08:00- 08:30 Hunan University Targeted Therapy in the Era of Molecular Medicine Prof. Dennis Discher 08:30-09:00 University of Pennsylvania From Polymersomes & Filomicelles to Foreign vs ‘Self’ Zhen Gu Plenary Prof. Timothy J. Deming Qiangbin Wang University of California, Los Angeles 09:00-09:30 Lectures Lintao Cai Use of Poly(methionine sulfoxide) to Impart Cell and Tissue Kanyi Pu Compatibility in Degradable Biomaterials Prof. Wim E. Hennink Utrecht University 09:30-10:00 Polymeric Nanoparticles for the Intracellular Delivery of

22 Morning 22 Morning Biotherapeutics 10:00-10:10 Coffee Break Prof. Samir Mitragotri 10:10-10:40 Harvard University August Plenary Understanding and Overcoming Biological Barriers for Drug Delivery Liangfang Zhang Lectures Prof. Ick Chan Kwon Zhuang Liu 10:40-11:10 Korea Institute of Science and Technology Nanoparticle-Based Photodynamic Imaging and Therapy of Cancer Closing Prof. Kazunori Kataoka The University of Tokyo 11:10-11:50 Honggang Cui Plenary Self-Assembled Supramolecular Nanosystems for Lecture Treating Cancer and Brain Disorders 11:50-12:20 Closing Ceremony Shen and Cui Lunch 资助单位：

浙江省自然科学基金委

浙江大学化学工程国家重点实验室浙江大学教育部生物工程重点实验室

冷泉港生物科技股份有限公司

富士光科技(苏州)有限公司

厦门福流生物科技有限公司

纳米医药研究整体解决方案

锘海生物科学仪器（上海）股份有限公司

13 Plenary Speakers

Dennis E. Discher University of Pennsylvania, Philadelphia, PA

Dennis E. Discher began at Penn in 1996, and is an elected member of the US National Academy of Engineering, the US National Academy of Medicine, and the American Association for the Advancement of Science. His lab focused first on physics of cell membranes, extending to drug delivery systems, and then discovered matrix elasticity effects on stem cell differentiation and the nucleus, with recent efforts on (i) DNA damage and genome variation in mechanobiology of cancer and development, and (ii) macrophage engineering to attack solid tumors. He earned his PhD from UC Berkeley & UC San Francisco, was an NSF International Fellow in computational biophysics at University of British Columbia, and holds appointments at Penn in Engineering & Applied Science as well as Graduate Groups in Physics and Pharmacology. Additional honors and service include the Friedrich Wilhelm Bessel Award from the Humboldt Foundation of Germany, past Chair of the NIH Gene & Drug Delivery Study Section, and member of the Editorial Board of Science.

15 From polymersomes & filomicelles to foreign vs ‘self’

Dennis E. Discher

From viruses to tissue matrices, biology is filled with remarkable polymeric structures that motivate mimicry with goals of at least clarifying and perhaps exploiting biological principles. Our development of vesicles made from block copolymers, ‘polymersomes’, began with analyses of molecular weight scaling and microphase transitions but soon turned to delivery of chemotherapeutic combinations against cancer (recently reviewed in [1]). Filamentous viruses (such as Influenza & Ebola) then inspired development and computations of flexible worm-like micelles – ‘filomicelles’ – that persist in the circulation and deliver better than spheres of the same polymer [2,3]. A chemo-differentiation cocktail that doesn’t just kill cancer cells but influences their phenotype seemed most effective in delivery. Regardless, particles of any type interact with innate immune phagocytes while nearby ‘Self’ cells are spared due to a polypeptide that limits phagocytic clearance [4]. The phagocyte’s cytoskeleton forcibly drives the decision downstream of adhesion, leading to a materials-inspired cell therapy [5]. Repeated dosing with the engineered macrophages is safe and effective but necessary in part because of pathways related to how matrix elasticity directs cell fates [6,7].

References: [1] Nair, et al. Polymersomes. Ch.26 in The Giant Vesicle Book, (2019). Taylor & Francis. [2] Geng, et al. Shape effects of filaments versus spherical particles in flow and drug delivery. Nature Nanotechnology (2007). [3] Nair, et al. Filomicelles deliver a chemo-differentiation combination of Paclitaxel and Retinoic Acid that durably represses carcinomas in liver to prolong survival. Bioconjugate Chemistry (2018). [4] Rodriguez, et al. Minimal 'Self' peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science (2013). [5] Alvey, et al. SIRPA-inhibited, marrow-derived macrophages engorge, accumulate, and differentiate in antibody-targeted regression of solid tumors. Current Biology (2017). [6] Engler, et al. Matrix elasticity directs stem cell lineage specification. Cell (2006). [7] Swift, et al. Nuclear Lamin-A Scales with Tissue Stiffness and Enhances Matrix-directed Differentiation. Science (2013)

16 Fernanda Ogochi Elsevier Publisher

Fernanda Ogochi is the Executive Publisher of Pharmacology and Pharmaceutical Sciences for Elsevier. She is responsible for the overall development and strategic direction of 10 scientific journals, including Journal of Controlled Release and Advanced Drug Delivery Reviews. She joined Elsevier in 2010, and has occupied several positions in the company in strategy and market intelligence. Prior to Elsevier, she worked 6 years in banking and in the health care industries in Brazil. Fernanda holds a BSc degree in Business Administration from the University of Sao Paulo (Brazil) and an MBA from the Tilburg University Business School (Netherlands).

17 How to get published in high impact journals, perspectives of the editor and the publisher

Fernanda Ogochi

Fuyao Zhang Shanghai Selection Bioscience Ltd.Co.

Fuyao Zhang Graduated from Chemistry Department of Zhejiang University in 1987 and obtained his Ph.D. in Polymer Science and Engineering in Zhejiang University under supervision of Professor Zhiquan Shen in 1992. After receiving his Ph.D. in 1992, he was appointed as a lecture in Zhejiang University and then was promoted to associate professor in Zhejiang University in 1994. In the same year, he was assigned to Aachen Technic University in Germany for cooperative research on polymer chemistry and materials in the Professor Whelm Keim’s laboratory. In 1995, he went to Hong Kong Polytechnic University to do research on asymmetric synthesis under guidance of Professor Albert SC Chan and earned his second Ph. D in Organic Chemistry in 1998. After that, he joined Professor E. J. Corey’s group at Harvard University, mainly engaged in novel methodology development and process development towards medicines. In 2001, Dr. Zhang joined Eli Lilly and Company as a scientist, senior scientist and principal scientist in the research and development of synthetic technology for clinical phase I-III drug candidates. In 2009, he returned to China and joined Jiangsu Hengrui Medicine Co., Ltd. and was appointed General Manager of Shanghai Unitris Biopharmaceutical Co., Ltd. In 2016, Dr. Zhang founded Shanghai Selection Bioscience Co., Ltd. and served as general manager of Shanghai Selection Bioscience Co., Ltd. Dr. Zhang has been appointed as visiting professor of Zhejiang University, Sun Yat-sen University, East China Normal University and Hong Kong Baptist University. He was honored as the American Minority Outstanding Scientist Award, the Young Researcher Award of the American Chemical Society, the Green Chemistry Award of Eli Lilly and Company and the President Award of Eli Lilly and Company. Dr. Zhang has extensive experience in research and development of new drugs, design of synthetic routes, route selection, process optimization and pilot scale-up, production and quality control of APIs, and application of green chemistry in pharmaceutical industry.

19 Establishment of transforming platform to accelerate nano-drugs research and development

Fuyao Zhang

Shanghai Selection Bioscience Ltd. Co. 576 Libing Road, Building 5, Floor 4, Shanghai Pudong, China, 201203 E-mail: [email protected]

The vision of Selection Bioscience is to establish a nano-drug R&D incubator and accelerator to accelerate the transformation of research findings from universities and research institutes into clinical development. This presentation will describe in detail how SelectionBio builds up the platforms for drug delivery system based on microspheres, liposomes and nano-particles, how SelectionBio enhances IND declaration for the drug candidates to enter the clinical development stage as soon as possible. This presentation will also share the SelectionBio's experience and insights in anti-cancer drug research and development, and share the successful stories of transforming nano-medicine research achievements from university into IND enabling application. SelecetionBio warmly welcomes the cooperation of nanodrug R&D from universities, research institutes and pharmaceutical companies.

He Tian Institute of Fine Chemicals, School of Chemistry East China University of Science & Technology,

He Tian received his Ph.D. degree from ECUST in 1989. He is an appointed Cheung Kong Distinguished Professor by the Education Ministry of China in 1999. He is a member of the Chinese Academy of Science and a Fellow of the World Academy of Sciences (TWAS) for the advancement of science in developing countries. He serves as Vice President of Chinese Chemical Society since 2019. His current research interests focus on the development of interdisciplinary materials science that determines the electronic and optical properties of materials.

21 Dynamic molecular fluorescent probes with assembling

He Tian

Institute of Fine Chemicals, School of Chemistry & Molecular Engineering, East China University of Science & Technology, Meilong Road 130, Shanghai 200237, China Email: [email protected]

Despite the rapid development of imaging techniques, precise probe localization and modulation in living cells is still a challenging task. This lecture mainly highlights the recent advances achieved in our laboratory in fabricating artificial dynamic-assembling systems for tuning emission colors and selective sensing biomarkers. For example, we show that the simple hybridization between a photochromic fluorescent glycoprobe and human serum albumin (HSA) enables a unique fluorescence “double-check” mechanism for precisely localizing and manipulating probe molecules in living cells. Docking of a carbohydrate-modified naphthalimide (Naph)-spiropyran (SP) dyad to a hydrophobic pocket of HSA produces the glycoprobe-protein hybrid, causing the protein conformation to fold as determined by small- angle X-ray scattering. We show that the Naph and merocyanine (the photoisomer of SP) fluorescence of the resulting hybrid can be reversibly switched by light in buffer solution and in target cells overexpressing the carbohydrate receptor. We also report the supramolecular host-guest inclusion of a “glycosylated” photoswitch to a serum protein forms the protein sensor capable of fluorescence- activatable sensing of a glycosidase activity in different cell models based on photochromic protein sensors. Importantly, the sensor can be used to monitor glycosidase activity in cancer cells and during cell aging with super-resolution microscopy thanks to its enhanced intracellular photochromic activity. In addition, we constructed fluorescent single ‘cursor’ to detect both aromatic and linear saturated dicarboxylate anions with different lengths and shapes incorporating a vibration-induced emission (VIE) phenazine core. Fluorescence titration studies revealed that treating DPAC-bisC4P with dicarbox-ylate guests capable of forming pseudo-macrocyclic host–guest complexes via multiple hydrogen bonding interactions be-tween the dicarboxylates and calix[4]pyrrole moieties, led to a blue-shift in the emission of the phenazine core. It highlights the potential benefits associated with combining a tunable VIE core with non-covalent binding interactions and thus sets the stage for the development of new fluorescent chemosensors where a single chemical entity responds to different analytes with a high level of tunability.

References: [1] Y. Fu, J. J. Zhang, X-P. He, B. L. Feringa, H. Tian, et al. J. Am. Chem. Soc. 2018, 140, 8671-8674. [2] Z. Y. Zhang, W. Song, J. H. Su, H. Tian, Adv. Funct. Mater. 2019, 29, 1902803

Ick Chan Kwon Korea Institute of science and Technology

Ick Chan Kwon is a Presidential Scholar at KIST-DFCI On-Site-Lab in Department of Cancer Biology, Dana Farber Cancer Institute Boston. He is a Tenured Principal Research Scientist of Korea Institute of Science and Technology (KIST). He received his B.S. and M.S. degrees in College of Engineering at Seoul National University and his Ph. D. in Pharmaceutics and Pharmaceutical Chemistry from University of Utah. After a post-doctoral training at CCCD in University of Utah, he joined KIST where he started his research on polymeric nanoparticle-based drug delivery system for antibiotics, anticancer drugs and gene therapy. He also pioneered in a research filed of Theragnosis, by combining molecular imaging and drug delivery system with smart nano-probes. He is a fellow of The Korean Academy of Science & Technology and a member of The National Academy of Engineering of Korea.

23 Nanoparticle-based photodynamic imaging and therapy of cancer

Ick Chan Kwon

KIST-DFCI On-Site-Lab, Department of Cancer Biology, Dana Farber Cancer Institute, Boston, USA Center for Theragnosis, Korea Institute of Science and Technology, Seoul, Korea. [email protected], [email protected]

1 Photodynamic therapy (PDT) utilizes reactive oxygen species ( O2) generated from photosensitizer after Near-Infrared (NIR) irradiation. PDT has been known as an effective therapeutic option owing to their minimal invasiveness as well as high selectivity by localized application of irradiation directly onto a disease site. Moreover, recent studies highlight that PDT-mediated immunogenic cell death (ICD) may also contributes to the therapeutic efficacy by utilizing body’s own immune system. However, most of PDT often suffers from unwanted side effects with unfavorable biodistribution and poor bioavailability of applied photosensitizers. Therefore, by utilizing enhanced permeation and retention (EPR) effect, nanoparticle-based PDT can improve cellular uptake, biodistribution and bioavailability. Recent studies on nanoparticle-based photodynamic imaging and therapy in our lab will be introduced and discussed in this talk.

Justin Hanes Johns Hopkins University

Justin Hanes is the Lewis J. Ort Endowed Professor of Ophthalmology and Director of the Center for Nanomedicine at the Johns Hopkins University, where he also holds faculty appointments in the departments of Biomedical Engineering, Chemical & Biomolecular Engineering, Neurosurgery, Oncology, and Pharmacology & Molecular Sciences. He is an inventor on more than 125 patents and patent applications focused in the area of advanced delivery systems that make drugs and gene therapies safer and more effective. Products based on these patents that have been approved by the US FDA are expected to help millions of patients suffering from Parkinson’s Disease or post-surgical ocular pain and inflammation. Dr. Hanes has co-founded 10 pharmaceutical companies, and they have more than 10 different drugs in ongoing or planned Phase 2 or 3 human clinical trials. He has served GrayBug Vision as President and CEO (2011-2013) and Chief Scientific Officer (2013-2015), Spiral Therapeutics as Chief Scientific Officer (2018-2019) and special advisor to the CEO (2019-present), and Blue Jay Biomedical as President and CEO (2019-present). He has been a member of the board of directors of Kala Pharmaceuticals (2009-2012), GrayBug Vision (2011-2019; Chair 2011-2015), Ashvattha Therapeutics (2015-2017), Orpheris (2015-2017), and Blue Jay Biomedical (Chair 2019-present). Justin is also a founder of Theraly Fibrosis (Acquired by D&D Pharma) and Neuraly (Acquired by D&D Pharma), and he is a Venture Partner with Camden Partners where he serves as the Chief Scientist of the Camden Partners Nexus Fund. The companies he has co-founded have raised more than five hundred million dollars in venture capital and through the public markets to bring innovative new therapies to patients suffering from diseases that affect vision, cognitive function, hearing, fibrosis and more. He has served on the scientific advisory boards for several companies, including Genentech (Drug Delivery Division), and he has served as chair of the Gene and Drug Delivery Study Section of the National Institutes of Health. Dr. Hanes was inducted into the National Academy of Inventors in 2014 and he has been elected fellow of the Controlled Release Society, American Association of Pharmaceutical Scientists (AAPS), and the American Institute of Medical and Biological Engineers. Awards he has received include the Ebert Prize from the AAPS, the Innovation in Biotechnology Award from the AAPS (twice), the Young Investigator Award from the Controlled Release Society, The CAREER Award from the National Science Foundation, the Clemson Award from the Society for Biomaterials, and multiple teaching awards from the Johns Hopkins University. He has been named among “The World’s Top 100 Young Innovators and Leaders in Technology and Business” by the MIT Technology Review, “The World’s Most Influential Scientific Minds” by Thompson Reuters (multiple times), an Edward C. Nagy Investigator by the National Institute of Biomedical Imaging and Bioengineering of the NIH, and a “Global Young Leader” by the US National Academy of Sciences. His degrees are in Chemical Engineering from UCLA (B.S. 1991) and MIT (Ph.D. 1996), and he completed a postdoctoral fellowship in Oncology and Neurosurgery at Johns Hopkins prior to joining the faculty of the Johns Hopkins University in 1998.

25 Nanomedicine: from concept to success in the clinic

Justin Hanes

This talk will cover the journey, from "beginning" (idea) to "end" (approved product to treat ocular pain and inflammation), of the "mucus-penetrating particle" technology developed in my laboratory at the Johns Hopkins University. It will also touch upon new clinical trials using this technology to treat dry eye disease. Ocular pain and inflammation due to ocular surgery affects millions of patients each year, as does dry eye disease. The talk will also provide new results from human clinical trials with a twice-per-year therapy for neovascular age-related macular degeneration, which is the most common cause of blindness in the elderly in the US.

Kazunori Kataoka The University of Tokyo

Kazunori Kataoka received his Ph.D. (1979) in Polymer Chemistry from The University of Tokyo. He started his academic career at Institute of Biomedical Engineering, Tokyo Women’s Medical College as Assistant Professor (1979) and was promoted to Associate Professor in 1988. He moved to Department of Materials Engineering, Tokyo University of Science in 1989 as Associate Professor and was promoted to full Professor in 1994. He then moved to Department of Materials Engineering, The University of Tokyo in 1998 as full Professor. He was appointed joint-position of full Professor at Center for Disease Biology and Integrative Medicine, The University of Toyo Medical School in 2004. In 2016, he took mandatory retirement from Graduate School of Engineering/Graduate School of Medicine, The University of Tokyo, and moved to the current position. He has been appointed as Adjunct Professor at Eshelman School of Pharmacy, University of North Carolina Chapel Hill since 2015, and as Director, Biomedical Insitute for Convergence at SKKU (BICS) at Sungyunkwan University, Korea since 2016. He has published over 500 peer-reviewed papers (H-index 130). He has been on the board of 15 international journals, including Editor of Journal of Biomaterials Science, Polymer Edition and Associate Editor of ACS Nano. His current major research interests include supramolecular materials for nanobiotechnology, focusing on drug and gene delivery systems.

27 Self-assembled supramolecular nanosystems for treating cancer and brain disorders

Kazunori Kataoka

Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, Kawasaki 210-0821, Japan; Institute for Future Initiatives, The University of Tokyo, Tokyo113-0033 [email protected] Nanotechnology-based medicine (Nanomedicine) has received progressive interest for the treatment of intractable diseases, such as cancer, as well as for the non-invasive diagnosis through various imaging modalities. Engineered polymeric nanosystems with smart functions play a key role in nanomedicine as drug carriers, gene vectors, and imaging probes. This presentation focuses present status and future trends of supramolecular nanosystems self-assembled from designed block copolymers for therapy and non- invasive diagnosis of intractable diseases. Nanosystems with 10 to 100 nm in size can be prepared by programmed self-assembly of block copolymers in aqueous entity. Most typical example is polymeric micelle (PM) with distinctive core-shell architecture. PMs have several properties relevant for nanosystems, including controlled drug release, tissue penetrating ability, and reduced toxicity1,2. Furthermore, smart functionalities, such as pH- and/or redox potential responding properties, can be integrated into the PM structure3. These smart PMs loaded with various chemotherapy reagents were evidenced to have a significant utility in the treatment of intractable and metastatic cancers, including pancreatic cancer4, glioblastoma5, and tumors harboring recalcitrant cancer stem cells (CSCs)6. Eventually, five different formulations of the PMs developed in our group have already been in clinical trials world-wide, including Japan, Asia, USA and European countries7. Versatility in drug incorporation is another relevant feature of supramolecular nanosystems for drug delivery. Small nucleic acid (SNA)-based medicine can be assembled into nanosytstems through the ionic interaction with oppositely-charged polycationic block copolymers8. In this way, siRNA- or antisense oligo (ASO)-loaded micellar or vesicular nanosystems were prepared, and their utility in molecular therapy of cancer has been revealed9-11. Downsizing of polyion complex (PIC) assembly comparable to the size of antibody allowed it to crossing physiological barrier, including a thick fibrotic stroma in pancreatic cancer and blood-brain tumor barrier in glioblastoma, exerting significant antitumor activity12. Furthermore, nanosysems hold promise for the treatment of intractable diseases other than cancer. Recently, we developed nanosystems decorated with glucose to crossing intact blood-brain barrier by recognizing glucose-transporter overexpressing on brain endothelial cells, indicating a novel route to deliver versatile drugs into brain for the treatment of neurodegenerative diseases, including Alzheimer’s disease13. [1] H. Cabral and K. Kataoka, J. Control. Rel. 190 (2014) 465-476; [2] Y. Matsumoto, et al, Nature Nanotech. 11 (2016) 533-538; [3] H. Cabral, K. Miyata, K. Osada, and K. Kataoka, Chem. Rev. 118 (2018) 6844-6892; [4] H. Cabral, et al, Nature Nanotech. 6 (2011) 815-823; [5] Y. Miura, et al, ACS Nano 7 (2013) 8583-8592; [6] H. Kinoh, et al, ACS Nano 10 (2016) 5643-5655; [7] N. Nishiyama, et al,

Kinam Park

Purdue University

Kinam Park received his Ph.D. degree in pharmaceutics from University of Wisconsin in 1983. After postdoctoral training in the Department of Chemical Engineering at the same university, he joined the faculty of College of Pharmacy, Purdue University in 1986. He has held a joint appointment in the Department of Biomedical Engineering since 1998. He became Showalter Distinguished Professor of Biomedical Engineering in 2006. His research focuses on oral delivery, drug-device combination products, and long-term microparticle formulations. He is the founder of Akina, Inc. specializing in polymers for drug delivery. He is currently the Editor-in-Chief of the Journal of Controlled Release.

29 PLGA Formulations: Understanding the complexity of the PLGA assay

Kinam Park

Purdue University, Weldon School of Biomedical Engineering & College of Pharmacy West Lafayette, IN 47907, U.S.A.

Poly(lactide-co-glycolide) (PLGA) has been the polymer of choice in many biomedical and pharmaceutical applications. Since the introduction of Lupron Depot in 1989 there are about 20 injectable, long-acting products, all of which are made of PLGAs. The primary reason to use PLGAs is that they have been used in the clinical products approved by the Food and Drug Administration of the U.S.A. (FDA). No other biodegradable polymers have been used in the FDA-approved products. Despite this, PLGAs have not been fully characterized, and their properties are still not clearly understood. The lack of detailed characterization methods presents challenges in the quality control and reproducibility of the PLGA formulations. It also presents difficulty in developing generic products that require the qualitative and quantitative (Q1/Q2) sameness against the reference listed drugs, or branded products. New assay methods have been developed for detailed characterization of PLGA properties, and they allow separation and characterization of PLGAs used in the FDA-approved products.

Leaf Huang

University of North Carolina at Chapel Hill

Leaf Huang. is the Fred Eshelman Distinguished Professor, Division of Pharmacoengineering and Molecular Pharmaceutics in the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill. Dr. Huang’s research has been in the area of gene therapy and targeted drug delivery. He has pioneered the liposome non-viral vector and has designed and manufactured the cationic lipid vector for the first non-viral clinical trial in 1992. His current work centers on nanoparticle vectors for gene transfer in tumor and liver. He also continues research in establishing a ligand targeted delivery system for cDNA, mRNA, siRNA, proteins and peptides for tumor growth inhibition and for vaccines in treating cancer and infected diseases. He has authored or co-authored more than 600 papers with an H-index of 121. He is also the inventor or co-inventor of 22 US and foreign patents. In 2004, he received the Alec D. Bangham MD FRS Achievement Award, which is the highest honor in liposome research. He was the recipient of the 2013 Distinguished Pharmaceutical Scientist Award which is the highest scientific recognition of the American Association of Pharmaceutical Scientists. Dr. Huang has also co-founded 6 biotech start-ups in the past.

31 Nanoparticles targeting tumor microenvironment for immunotherapy

Leaf Huang

Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA The importance of the microenvironment in tumor growth and metastasis is well appreciated. We have previously discovered that tumor associated fibroblasts, similar to the tumor cells, highly express sigma-1 receptor to which aminoethyl anisamide (AEAA) is a high affinity ligand. Using AEAA as a targeting ligand, we have delivered genes and drugs to both the tumor cells and TAFs. Expression of relaxin in the TME is effective in deactivating hepatic stellate cells and inhibit fibrosis and metastasis in the liver. Expression of traps (antibody-like fusion proteins) in the TME also greatly remodel the immune microenvironment of the tumor. Delivery of small molecules, especially those selected from the traditional Chinese medicines, induces immunogenic cell death of the tumor cells and facilitate immunotherapy. These approaches will be highlighted in the talk. Work supported by NIH grant CA198999.

Nicholas A. Peppas University of Texas at Austin

Nicholas A. Peppas is the Cockrell Family Regents Chair in the Departments of Chemical Engineering, Biomedical Engineering, Surgery and Molecular Pharmaceutics of the University of Texas at Austin. His work in biomaterials, polymer physics, drug delivery and bionanotechnology follows a multidisciplinary approach by blending modern molecular and cellular biology with engineering principles to design the next-generation of medical systems and devices for patient treatment. Over the past 44 years he has set the fundamentals and rational design of drug delivery systems and developed models of drug and protein diffusion in controlled release devices and biological tissues. In 2012 he received the Founders Award of the National Academy of Engineering and in 2018 the Adam Yarmolinsky Award from the National Academy of Medicine. In 2008, AIChE named him on of the One Hundred Chemical Engineers of the Modern Era. Peppas is a member of the National Academy of Engineering, the National Academy of Medicine, the American Academy of Arts and Sciences, the National Academy of Inventors, the Chinese Academy of Engineering, the Canadian Academy of Engineering, the National Academy of France, the Royal Academy of Spain, the Academy of Athens and the Academy of Texas. He has been recognized with awards from AIChE (Founders Award, William Walker Award, Institute Lecture, Jay Bailey Award, Bioengineering Award, Materials Award), the Biomedical Engineering Society (Distinguished Scientist Award), the American Institute of Medical and Biological Engineering (Galletti Award), the Society for Biomaterials (Founders, Clemson and Hall Awards), the Controlled Release Society (Founders, Heller and Eurand Awards) and other societies. He has served as President of the International Union of Societies of Biomaterials Science and Engineering, Chair of the Engineering Section of the American Association for the Advancement of Science, and President of the Society for Biomaterials and the Controlled Release Society. He is deputy Editor of Science Advances. He has supervised the research of 115 PhDs and about 180 postdocs and visiting scientists. Peppas holds a Dipl. Eng. from the NTU of Athens (1971), a Sc.D. from MIT (1973), and honorary doctorates from the Universities of Ghent, Parma, Athens, Patras, Ljubljana, Thessaloniki, Santiago de Compostela, and the Technical University of Athens. In China, he is an Honorary Professor at Sichuan University, Beihang Universiy, PLA Hospital and Medical School, and Peking Medical Union College.

33 Molecular recognition at the nanoscale level

Nicholas A. Peppas.

Fletcher Stuckey Pratt Chair in Engineering Professor of Biomedical Engineering, Chemical Engineering, Pharmacy and Medicine Director of Center on Biomaterials, Drug Delivery, and Bionanotechnology The University of Texas at Austin

In recent years several groups have started designing advanced hybrid systems that can provide recognition of the causes of various diseases. These systems are based on biomaterials that can be deigned to recognize various undesirable analytes and inform the medical practitioner of the early stages of a disease. This revolutionary method of detection is based on engineering principles, good materials properties and interaction in “real” systems. Recent developments in protein delivery have been directed towards the preparation of targeted formulations for protein delivery to specific sites, use of environmentally-responsive polymers to achieve pH- or temperature-triggered delivery, usually in modulated mode, and improvement of the behavior of their mucoadhesive behavior and cell recognition. We address design and synthesis characteristics of novel biomaterials capable of protein release as well as artificial molecular structures capable of specific molecular recognition of biological molecules. With such systems we can prepare biomimetic materials for intelligent drug delivery, drug targeting, and tissue engineering.

Paul S. Weiss

University of California, Los Angels

Paul S. Weiss graduated from MIT with S.B. and S.M. degrees in chemistry in 1980 and from the University of California at Berkeley with a Ph.D. in chemistry in 1986. He is a nanoscientist and holds a UC Presidential Chair and a distinguished professor of chemistry & biochemistry, bioengineering, and materials science & engineering at UCLA, where he was previously director of the California NanoSystems Institute. He also currently holds visiting appointments at Harvard’s Wyss Institute and several universities in Australia, China, and South Korea. He studies the ultimate limits of miniaturization, developing and applying new tools and methods for atomic-resolution and spectroscopic imaging and patterning of chemical functionality. He and his group apply these advances in other areas including neuroscience, microbiome studies, and high-throughput gene editing. He led, coauthored, and published the technology roadmaps for the BRAIN Initiative and the U.S. Microbiome Initiative. He has won a number of awards in science, engineering, teaching, publishing, and communications. He is a fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, the American Chemical Society, the American Institute for Medical and Biological Engineering, the American Physical Society, the American Vacuum Society, the Canadian Academy of Engineering, the Materials Research Society, and an honorary fellow of the Chinese Chemical Society. He is the founding and current editor-in-chief of ACS Nano.

35 Adding the chemical dimension to lithography at all scales: enabling cellular therapies & other adventures in biology and medicine

Paul S. Weiss California NanoSystems Institute and Departments of Chemistry & Biochemistry, Bioengineering, and Materials Science & Engineering, UCLA, Los Angeles, CA 90095 By controlling the exposed chemical functionality of materials from the submolecular through the centimeter scale, we have enabled new capabilities in biology, medicine, and other areas. I will discuss current and upcoming advances and will pose the challenges that lie ahead in creating, developing, and applying new tools using this capability. These advances include using biomolecular recognition in sensor arrays to probe dynamic chemistry in the brain and microbiome systems. In other areas, we introduce biomolecular payloads into cells for gene editing at high throughput for off-the-shelf solutions targeting hemoglobinopathies, immune diseases, and cancers. We circumvent the need for viral transfection and electroporation, both of which have significant disadvantages in safety, throughput, cell viability, and cost. Mechanical deformation can make cell membranes transiently porous and enable gene-editing payloads to enter cells. These methods use specific chemical functionalization and control of surface contact and adhesion in microfluidic channels.

Pep Pàmies Editor-in-chief, Nature biomedical engineering

Pep Pàmies is leading the editorial team of Nature Biomedical Engineering, a journal from the Nature family that launched in January 2017. Pep was an editor for Nature Materials for more than 5 years, where he championed the biomaterials content, handling manuscripts and commissioning articles in a wide variety of subjects, including tissue engineering, medical imaging, regenerative medicine, cancer therapy and diagnostics. Previously, Pep conducted research in computational soft matter and biophysics at Columbia University's Chemistry Department in New York City, at the Max Planck Institute of Colloids and Interfaces in Potsdam, and at the Atomic and Molecular Physics Institute in Amsterdam. Pep obtained a PhD in Chemical Engineering in December 2003 from Rovira i Virgili University in Catalonia, Spain.

37 Biomedical engineering for improving human health

Pep Pàmies

Launched in January 2017, Nature Biomedical Engineering publishes original research, reviews and commentary of high significance to the biomedical engineering community, including bench scientists interested in devising materials, methods, technologies or therapies to understand or combat disease; engineers designing or optimizing medical devices and procedures; and clinicians leveraging research outputs in biomedical engineering to assess patient health or deliver therapy across a variety of clinical settings and healthcare contexts.

In this discussion, the Chief Editor will convey the journal’s role in accelerating research in biomedical engineering, with a focus on nanomedicine and nanobiotechnology. He will argue that leading bioengineering journals should showcase the value that they provide to the communities they serve, empower researchers to help them advance discovery and technology for improving human health, and actively steer research communities towards better reporting standards, increased data sharing, more valuable scientific outputs and stories, and the most promising technological and translational solutions.

Samir Mitragotri Harvard University

Samir Mitragotri is the Hiller Professor of Bioengineering and Wyss Professor of Biologically Inspired Engineering at Harvard University. Prior to this, he was the Mellichamp Chair Professor in the Department of Chemical Engineering at the University of California, Santa Barbara. His research is focused on transdermal, oral, and targeted drug delivery systems. He is an elected member of the National Academy of Engineering, National Academy of Medicine and National Academy of Inventors. He is also a foreign member of Indian National Academy of Engineering. He is also an elected fellow of AAAS, CRS, BMES, AIMBE, and AAPS. He is an author of over 275 publications, an inventor on over 180 patent/patent applications, and a Thomson Reuters Highly Cited Researcher. He received his BS in Chemical Engineering from the Institute of Chemical Technology, India and a PhD in Chemical Engineering from the Massachusetts Institute of Technology. He is the Editor-in-Chief of AIChE’s and SBE’s new journal Bioengineering and Translational Medicine.

39 Understanding and overcoming biological barriers for drug delivery

Samir Mitragotri

Effective delivery of drugs is a major problem in today’s healthcare. At a fundamental level, the challenge of drug delivery reflects the fact that the drug distribution in the body is limited by body’s natural metabolic processes and transport barriers. These biological barriers, while serving an important purpose of regulating body’s metabolic functions, limit the drug dose that ultimately reaches the target site. Accordingly, many drugs fail to reach their full therapeutic potential. Our research aims at developing a fundamental understanding of body’s key biological barriers such as skin, intestinal epithelium and the immune system, and utilizing this understanding to develop novel means to negotiate these barriers to deliver drugs. Our research has led to the understanding of how transport properties of biological barriers can be modulated to deliver drugs in effective ways for the treatment of diseases such as diabetes and cancer, among others. I will present an overview of the lessons learned from our exploration of these biological barriers.

Shuming Nie University of Illinois at Urbana-Champaign

Shuming Nie is the Grainger Distinguished Chair in Engineering, Professor of Bioengineering, Chemistry, Materials Science and Engineering, Electrical and Computer Engineering at the University of Illinois at Urbana-Champaign, and Founding Dean of the College of Engineering and Applied Sciences at Nanjing University (China). His academic research is in the areas of nanomedicine; image- guided cancer surgery; cell-based immunotherapy; wearable optoelectronic devices and digital health. His major academic achievements include the discovery of colloidal metal nanoparticles that are able to amplify the efficiencies of surface-enhanced Raman scattering (SERS) by 14-15 orders of magnitude, his pioneering work on water-soluble semiconductor quantum dots for biomedical applications, and his breakthrough work in developing multifunctional smart nanoparticles for integrated biomedical imaging and therapy, including image-guided cancer surgery. Professor Nie has published over 350 papers, patents, and book chapters, have delivered more than 500 invited lectures around the world, and have trained over 30 doctoral students and postdoctoral fellows who are now making an impact at top academic institutions and biotech companies. His scholarly work has been cited 66,000 times according to Google Scholar. Professor Nie received his BS degree from Nankai University (China) in 1983, earned his MS and PhD degrees from Northwestern University (Evanston, Illinois, 1984-1990), and did postdoctoral research at Georgia Institute of Technology and Stanford University (1990-1994).

41 Nanotechnology: from single-molecule raman spectroscopy to image- guided cancer surgery

Shuming Nie

Departments of Bioengineering, Chemistry, Materials Science and Engineering, Electrical and Computer Engineering, Beckman Institute, Micro/Nanotechnology Lab, and the Institute for Genomic Biology, University of Illinois at Urbana- Champaign, 1406 W. Green Street, 2116 Everitt Lab, IL 61801 Email: [email protected]

Nanotechnology is an area of considerable current interest in chemistry, engineering, and medicine because of its broad applications in molecular imaging, in-vitro diagnostics, targeted therapy, and image- guided surgery. The basic rationale is that nanometer-sized particles such as quantum dots, colloidal gold, and polymeric nanomicelles have functional and structural properties that are not available from either discrete molecules or bulk materials. When conjugated with targeting ligands such as monoclonal antibodies, peptides or small molecules, these nanoparticles can be used to target malignant tumor cells and the tumor microenvironment (such as tumor stroma and tumor vasculatures) with high specificity and affinity. In the “mesoscopic” size range of 10-100 nm, nanoparticles also have large surface areas for conjugating to multiple diagnostic and therapeutic agents, opening new possibilities in imaging, therapy, and surgery. At the present, however, there are several fundamental problems and technical barriers that must be understood and overcome. In this talk, I will discuss the major challenges and opportunities in the development of technology for single-molecule spectroscopy, intraoperative cancer detection, and image-guided precision surgery. This work was supported by grants from the US National Institutes of Health (U54 CA119338, RC2 CA148265, and R01CA163256).

Timothy J. Deming University of California, Los Angeles.

Timothy J. Deming received a B.S. in Chemistry from the University of California, Irvine in 1989, and graduated with a Ph.D. in Chemistry from the University of California, Berkeley, in 1993. After a NIH postdoctoral fellowship at the University of Massachusetts, Amherst with David Tirrell, he joined the faculty in the Materials Department at the University of California, Santa Barbara in 1995. Here he held appointments in the Materials and Chemistry Departments where he was promoted to Associate Professor in 1999 and Full Professor in 2003. His appointment is now as Professor of Bioengineering and Professor of Chemistry and Biochemistry at the University of California Los Angeles. He served as the Chairman of the Bioengineering Department at UCLA from 2006 to 2011. He is a leader in the fields of polypeptide synthesis, self-assembly of block copolypeptides, and use of polypeptides in biology, for which he has received awards from the National Science Foundation, the Office of Naval Research, The Arnold and Mabel Beckman Foundation, the Alfred P. Sloan Foundation, the Camille and Henry Dreyfus Foundation, the Materials Research Society, and the IUPAC Macromolecular Division. He is a Fellow of the American Institute of Medical and Biological Engineering, and recently received the Fulbright- Tocqueville Distinguished Chair Award. Research in the Deming lab is focused on synthesis, processing, characterization and evaluation of biomimetic materials based on polypeptides. These materials are being studied since they can be prepared from renewable resources, can be biocompatible and biodegradable, and possess unique self-assembling properties. The Deming lab develops new synthetic materials with properties that rival the complexity found in biological systems. Our emphasis is on development of new synthetic methodologies as well as the use of biological precedents and strategies for the design of new materials. Our lab continues to take on significant new challenges in the exploration of applications of our materials for interaction with biological systems and for medicine, as well as development of new economical and scalable preparative routes to more complex and functional polypeptide architectures.

43 Use of poly(methionine sulfoxide) to impart cell and tissue compatibility in degradable biomaterials

Timothy Deming

Chemistry and Biochemistry Department and Bioengineering Department, UCLA

Our lab has developed synthetic methods that allow a robust variety of modifications to the thioether containing side-chains in methionine residues. One modification is the mild oxidation of hydrophobic, -helical poly(methionine) to hydrophilic, conformationally disordered poly(methionine sulfoxide). This polymer was found to possess non-fouling properties similar to PEG, but is also degradable and capable of being reduced back to methionine within cells. We report on the development of self- assembled biomaterials, such as vesicles and hydrogels, incorporating poly(methionine sulfoxide) as the solvent exposed hydrophilic segments. The use of these finely tuned hydrogel formulations for study of central nervous system biology will be presented.

Weihong Tan Hunan University

Weihong Tan earned his Ph.D. in Physical Chemistry at the University of Michigan in 1992. He stared his academic position in 1995 at University of Florida after doing a Distinguished Postdoctoral Fellow at Ames Lab, US-DOE. He was promoted to associate professor in 2001 and full professor in 2003. He started his research activity at Hunan University in 2010. Prof. Tan’s research is in the general area of Bioanalytical Chemistry, Chemical Biology, and Molecular Medicine. He specializes in aptamer research and DNA nanotechnology as well as cancer theranostics. He has published over 650 peer-reviewed scientific papers. According to Thomson Reuters, he is among the small, prestigious group of Highly Cited Researchers for the period between 2014-2018. His H index is 133. He is currently an Associate Editor for JACS (Journal of American Chemical Society). He has received over thirty awards and honors, including the Award in Spectrochemical Analysis from American Chemical Society in 2018, the He Liang He Li Foundation Award in Science and Technology in 2018, the Ralph Adams Award for Bioanalytical Chemistry in 2019 and The Pittsburgh Analytical Chemistry Award in 2019. Beckman Young Investigator Award in 1997, the Pittcon Achievement Award in 2004, He was elected as an AAAS Fellow in 2005, an Academician of the Chinese Academy of Sciences in 2015, an Academician of the World Academy of Sciences in Developing Countries in 2016.

45 Targeted therapy in the era of molecular medicine

Weihong Tan

1Molecular Sciences and Biomedicine Laboratory (MBL), State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences and Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China

2Institute of Cancer and Basic Medicine, Chinese Academy of Sciences; Cancer Hospital, University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

The era of molecular medicine requires diagnosis and treatment of diseases at the molecular level. Today, in cancer treatment, chemotherapy is a very important treatment in addition to surgery. The use of small molecule anticancer drugs can effectively prevent or slow the growth of tumors. However, a large number of small molecule anticancer drugs do not have the ability to recognize cancer cells, while also act on normal cells, resulting in great toxic side effects. As the essence of modern precision medicine, the development of cancer-targeted drugs has attracted widespread attention. This technology is the most effective way to reduce the toxic side effects of small molecule anticancer drugs on the body and improve the overall efficacy. After decades of development, antibody-drug conjugates (ADCs) have been developed and used in targeted cancer therapies. However, some of the limitations such as uncontrollable drug quality; immature drug release mechanisms; low cell penetration efficiency; complex production processes, limit the rapid development of this field. Therefore, how to develop a new cancer-targeted therapeutic drug is an urgent problem to be solved in this research field. Nucleic acid aptamers are called “chemical antibodies” and have similar targeting and binding ability to antibodies. In addition, the nucleic acid aptamers have many advantages such as high stability, low immunogenicity, low production cost, and easy chemical modification. The development of nucleic acid aptamer-based cancer targeting drug-aptamer drug-conjugate (ApDC) can effectively overcome the inherent limitations of antibody-drug conjugates, and has important significance in medical research and clinical application prospects. We will introduce the principles, preparation and wide application of ApDC in this report. At the same time, we will introduce the possible important role of ApDC in the modernization of traditional Chinese medicine.

Key words: aptamers, aptamer drug-conjugate (ApDC), molecular medicine, targeted therapy, cancer

Wim E. Hennink Utrecht University

Wim E. Hennink obtained his Ph.D. degree in 1985 at the Twente University of Technology on a thesis with a biomaterials research topic. From 1985 until 1992 he had different positions in the industry. In 1992 he was appointed as professor at the Faculty of Pharmacy of the University of Utrecht. From 1996 on he is head of the Pharmaceutics division. At present he is the head of the Department of Pharmaceutical Sciences, Utrecht University. And he is the special issue editor for Journal of Controlled Release. His main research interests are in the field of polymeric drug delivery systems. He published over 577 papers and book chapters and is the inventor of 20 patents.

Polymeric Nanoparticles for the Intracellular Delivery of Biotherapeutics

Wim E. Hennink

Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands Many biotherapeutics among which nucleic acid based drugs, pharmaceutical proteins and antigens, have to be delivered intracellularly to exert their biological effects. However, these therapeutics, because of their hydrophilic character and large size, do not spontaneously pass cellular membranes. An attractive approach to deliver these therapeutic in the target cell is to load them in nano-sized carriers. As first example, we designed reduction-sensitive cationic dextran nanogels in which an antigen (ovalbumin, OVA) was reversibly immobilized to the hydrogel network via disulfide bonds. These bonds are stable in the extracellular environment but are cleaved in the cytosol of dendritic cells due to the presence of glutathione resulting in triggered released of the loaded antigen. These OVA-loaded nanogels indeed showed intracellular release of OVA up on internalization by DCs and subsequently boost the MHC class I antigen presentation leading to activation of T-cells. In a prophylactic model, 90% of the mice vaccinated with OVA conjugated nanogels + poly I:C) as adjuvant were protected against tumor formation for 55 days. In a therapeutic model, 40% of the mice eliminated their tumor cells, which was remarkable compared to other groups in which none of the mice showed tumor cell killing [1, 2]. In another approach, cationic polymers containing either azide or strained alkyne groups were synthesized as electrostatic glue which complexed charged single stranded RNA (PolyU) to form a self- crosslinked polyplex core. An azide-modified model antigen (ovalbumin, OVA) and a BCN-modified

47 mannosylated or galactosylated polymer were sequentially conjugated to the RNA core via disulfide bonds using copper free click chemistry to form the shell of the polyplexes. The generated reducible virus mimicking particles (VMPs) with a diameter of 200 nm and negatively surface charge (−14 mV) were colloidally stable in physiological conditions. The mannosylated VMPs (VMP-Man) showed 5 times higher cellular uptake by bone marrow derived DCs (BMDCs) compared to their galactosylated VMP (VMP-Gal) counterpart. Moreover, VMPMan efficiently activated DCs and greatly facilitated MHC I Ag presentation in vitro. Vaccination of mice with VMP-Man elicited strong OVA-specific CTL responses as well as humoral immune responses [3]. Recently, we reported on PEGylated NPs based on a hydroxylated PLGA polyester for the selective delivery of saporin, a cytotoxic protein, in the cytosol of HER2 positive cancer cells. This selective uptake was achieved by decorating the surface of the NPs with the 11A4 nanobody that is specific for the HER2 receptor. Confocal microscopy observations showed rapid and extensive uptake of the targeted NPs (11A4-NPs) by HER2 positive cells, but not by HER2 negative cells. Importantly, a dose dependent cytotoxic effect was only observed on HER2 positive cells when these were treated with saporin-loaded 11A4-NPs in combination with photochemical internalization (PCI), a technique that uses a photosensitizer and local light exposure to facilitate endosomal escape of entrapped nanocarriers and biomolecules. The combined use of saporin-loaded 11A4-NPs and PCI strongly inhibited cell proliferation and decreased cell viability through induction of apoptosis. These results suggest that the combination of the targeting nanobody on the NPs with PCI are effective means to achieve selective uptake and cytotoxicity of saporin loaded NPs [4]. In conclusion, polymeric nanoparticles are attractive carrier systems for the targeted intracellular delivery of biotherapeutics.

REFERENCES 1. Li D, Kordalivand N, Fransen MF,Ossendorp F, Raemdonck K, Vermonden T, Hennink WE, and van Nostrum CF. Reduction-sensitive dextran nanogels aimed for intracellular delivery of antigens. Advanced Functional Materials 25, 2993-3003, 2015 2. Li D, Sun F, Bourajjaj M, Chen Y, Pieters EH, Chen J, van den Dikkenberg JB, Lou B, Camps MG, Ossendorp F, Hennink WE, Vermonden T, and van Nostrum CF. Strong in vivo antitumor responses induced by an antigen immobilized in nanogels via reducible bonds. Nanoscale 8, 19592-19604, 2016. 3. Lou B, De Beuckelaer A, Boonstra E, Li D, De Geest B, De Koker S, Mastrobattista E, Hennink WE. Modular core-shell polymeric nanoparticles mimicking viral structures for vaccination. Journal of Controlled Release 293, 48-62, 2019. 4. Martínez-Jothar L, Beztsinna N, van Nostrum CF, Hennink WE, and Oliveira S. Selective cytotoxicity to HER2 positive breast cancer cells by saporin-loaded nanobody-targeted polymeric nanoparticles in combination with photochemical internalization. Molecular Pharmaceutics 16, 1633-1647, 2019.

Xi Zhang

Jilin University & Tsinghua University

Xi Zhang received B.Sc. in Analytical Chemistry, M.Sc. and Ph.D degrees in Polymer Chemistry and Physics at Jilin University under the supervision of Prof. Jiacong Shen and Prof. Helmut Ringsdorf (Johannes Gutenberg-Universität Mainz). He joined the Department of Chemistry at Jilin University as a lecturer in 1992 and was then promoted to be a professor in 1994. He got Changjiang special professorship from Ministry of Education in 1999. He moved to Tsinghua University in 2003. Currently, he serves as the President of Jilin University; Director of Polymer Division, Chinese Chemical Society; Editor-in-Chief of Acta Polymerica Sinica; and Executive Editor-in-Chief of CCS Chemistry. He was elected as a Member of Chinese Academy of Sciences (2007), RSC Fellow (2008), and ACS Fellow (2016). His main scientific interests are in the interdisciplinary areas of supramolecular chemistry and polymer chemistry, including supramolecular polymers, supramolecular chemotherapy, supramolecular free radicals, supra-amphiphiles, Se-containing polymers, organized molecular films, and single- molecule force spectroscopy.

49 Supramolecular phototherapy

Xi Zhang

Department of Chemistry, Tsinghua University, Beijing 100084, China E-mail: [email protected] Phototherapy, including photodynamic therapy and photothermal therapy, is an indispensable light- induced method for cancer therapies and curing bacterial infections.[1] Even though phototherapy has been utilized in clinical applications, it possesses some shortcomings such as side effects to normal tissues and relatively low efficiencies.[2] Supramolecular phototherapy aims to employ supramolecular strategies for tuning the activity and selectivity of photoactive reagents, thus improving the efficiency of phototherapy. We employed the steric effect of cucurbit[7]uril (CB[7]) to diminish the aggregation of a porphyrin derivative through host-guest complexation. By forming the supramolecular photosensitizer, the singlet oxygen quantum yield was greatly increased owing to the suppression of self-quenching. As a result, the supramolecular photosensitizer showed a significantly improved antibacterial activity under mild white light irradiation and a highly efficient antibacterial photodynamic therapy could be achieved.[3] We also employed the electrostatic effect of the carbonyl groups of CB[7] to stabilize the radical anion of a derivative of naphthalene diimide (NDI). The supramolecular NDI radical anion generated through PET process displayed a higher yield and longer lifetime.[4] When NDI was replaced by perylene diimide (PDI), the supramolecular PDI radical anion became an effective near infrared system with enhanced photothermal conversion efficiency.[5] It was interestingly found that the supramolecular complex of PDI and CB[7] could be selectively reduced to form the supramolecular PDI radical anion by facultative anaerobic bacteria, for example, E. coli. Therefore, the selective antibacterial activity of the supramolecular complex could be realized by the efficient photothermal conversion of the supramolecular PDI radical anion under near-infrared irradiation.[6] It is highly anticipated that supramolecular strategies can be extended to many other photoactive reagents. Moreover, the method of supramolecular phototherapy may be applied in anticancer treatments, thus bringing a new horizon of phototherapy. References [1] S. G. Bown, Phototherapy of Tumors, World J. Surg. 7 (1983) 700-709. [2] X. Li, H. Bai, Y. Yang, J. Yoon, S. Wang, X. Zhang, Supramolecular Antibacterial Materials for Combatting Antibiotic Resistance, Adv. Mater. 31 (2019) 1805092. [3] K. Liu, Y. Liu, Y. Yao, H. Yuan, S. Wang, Z. Wang, X. Zhang, Supramolecular Photosensitizers with Enhanced Antibacterial Efficiency, Angew. Chem. Int. Ed. 52 (2013) 8285-8289. [4] Q. Song, F. Li, Z. Wang, X. Zhang, A Supramolecular Strategy for Tuning the Energy Level of Naphthalenediimide: Promoted Formation of Radical Anions with Extraordinary Stability, Chem. Sci. 6 (2015) 3342-3346. [5] Y. Jiao, K. Liu, G. Wang, Y. Wang, X. Zhang, Supramolecular Free Radicals: Near-Infrared Organic Materials with Enhanced Photothermal Conversion, Chem. Sci. 6 (2015) 3975-3980. [6] Y. Yang, P. He, Y. Wang, H. Bai, S. Wang, J.-F. Xu, X. Zhang, Supramolecular Radical Anions Triggered by Bacteria in situ for Selective Photothermal Therapy, Angew. Chem. Int. Ed. 56 (2017) 16239-16242.

Yuliang Zhao National Center for Nanosciences and Technology, China

Yuliang Zhao is Professor of Chemistry, Chinese Academy of Sciences, the Director-General, National Center for Nanosciences and Technology, China. He graduated from Sichuan Univ. in 1985, and received PhD at Tokyo Metropolitan Univ. in 1999. He moved to Chinese Academy of Sciences from RIKEN in 2001. Research Interest: He proposed the toxicity study of engineered nanomaterials in 2001, and is a pioneer with innovative ideas for initiating the study on nanosafety issues. His work focuses on biological effects/activities of nanomaterials with an emphasis on the establishment of reliable and valid analysis methods for discovering the biological effects of nanomaterials/nanomedicines in vivo, understanding of the chemical mechanisms of nanosafety and safe application of nanomaterials. These have led to an ISO standard analytical method being adapted by ISO/IEC 168 member countries, the establish nanosafety assessment framework for occupational exposure of nanomaterials, the discovery of a new-concept nanomedicine for cancer therapeutics, etc. Before 2001, he and colleagues in Japan discovered the Element 113 (Nh) which is first new element that has been discovered in Asia and filled in the Element Periodic Table. Publications: He published ~580 peer-review scientific papers, 8 editorials in international journals, with citation by >40,000 times (H-index 101); edited and published 13 books (3 books in English and 10 in Chinese), with his earliest efforts on systematizing the knowledge for nanosafety in category of nanomaterials, and made significant contribution to building the knowledge framework for nanosafety issue. Invited/Plenary Lectures: He delivered > 330 plenary and invited lectures at conferences, universities/institutes worldwide. He was invited to serve as a nanosafety expert/advisor by UNEP (United Nations, 2006), OECD (Nanosafety Team, 2006), Finland (2010), France (2009), Canada (2007), etc. Prize/Awards: The elected Member of TWAS (2018), the Academician of CAS (2017), TWAS Prize in Chemistry (2016), National Prize for Natural Sciences (2012, 2018), China Award for Outstanding Contribution on Toxicology (2015), the 60 Years Achievement of Chinese Academy of Sciences (2009); Beijing Award for Leading Talent in Science & Technology (2014), etc. Chinese Academy of Sciences-Bayer Young Scientist Award (2006), Beijing Award for Science and Technology (2008), the National Natural Science Fund for Distinguished Young Scholars (2005), etc.

51 Mechanisms of nanotoxicity and nanomedicine

Yuliang Zhao

National Center for Nanoscience and Technology of China, and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences (CAS) Email: [email protected], or [email protected] The biological effects and activities of nanomaterials (nanoparticles) are fundament related to many newly emerging frontier sciences of multidisciplinary fields, e.g., nanomedicine, nanotoxicology, biomedical materials, nanobioanalytical chemistry, nanobiotechnology, nanobiomedical engineering, ecology nanotechnology, cancer nanotechnology, nanochemistry, etc. So far, the key discoveries for nanomaterials/nanomedicines interacting with biosystems include, (A) nanomaterials/nanomedicines maybe a best way for human`s complex diseases like cancer or human chronic diseases; (B) nanomaterials/nanomedicines may be candidate for development of the next generation of medicine, called as nanomedicine; (C) nanomaterials/nanomedicines easily penetrate biological barriers; (D) nanomaterials/nanomedicines easily adsorb blood proteins to form protein corona; (E) nanomaterials/nanomedicines easily cross cell membrane to enter cells and induce intracellular ROS generation; (F) Nanosizes and nanosurface chemistry largely determine the fate of nanomaterials/nanomedicines in vivo, etc. In the talk, we will discuss the systematic studies on nanotoxicity and the newly understanding of nanotoxicological mechanism of above observations, and its application in cancer nanomedicine to achieve potent antitumor activity and minimal in vivo adversity. An example gives by a recent study in development of DNA nanorobots as intelligent nanomedicines to regulate tumor microenvironment to block tumor microvessels or re-store the homeostasis of tumor stroma. Both proved to be safe and immunologically inert for use in normal mice and Bama miniature pigs, and represents a promising strategy for precise drug design for cancer therapeutics. References [1] Li S.P., Jiang Q., Liu S.L., Zhang Y.L., Tian Y.H., Song C., Wang J., Zou Y.G., Anderson G.J., Han J.Y., Chang Y., Liu Y, Zhang C., Chen L, Zhou G.B., Nie G.J., Yan H., Ding B.Q., Zhao Y.L., Drugging the Undrugifyable: a Therapeutic DNA Nanorobot with On-target Tumor Infarction for Cancer Therapy, Nature Biotechnology, 36 (2018), doi:10.1038/nbt.4071. [2] Han X.X, Li Y.Y, Xu Y., Zhao X., Zhang Y., Yang X., Wang Y., Zhao R.F., Anderson G.J., Zhao Y. L., Nie G.J., Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem. Nature Communication., 9 (2018): 3390. doi: 10.1038/s41467-018-05906-x. [3] Li S.P., Zhang Y.L., Wang J., Zhao Y., Ji T.J., Zhao X., Ding Y.P., Zhao X.Z., Zhao R.F, Li F., Yang X., Liu SL., Liu Z.F., Lai J.H., Whittaker A. K., Anderson G.J., Wei J.Y., Nie G.J., Nature Biomedical Engineering, 2018, doi: 10.1038/s41551-017-0125-6. [4] Wang L.M, Yan L, Liu J, Chen C.Y, and Zhao Y.L, Quantification of Nanomaterial/ Nanomedicine Trafficking in Vivo, Analytical Chemistry, 90 (2018), 589-614. Cancer Sci. 107 (2016) 867-874; [8] K. Miyata, et al, Chem. Soc. Rev. 41 (2012) 2562-2574; [9] Y. Yi, et al, J. Control. Rel. 295 (2019) 268-277; [10] K. Katsushima, et al, Nature Commun. 7 (2016) 13616; [11] B.-S. Kim, et al, J. Amer. Chem. Soc. 141 (2019) 3699; [12] S. Watanabe, et al, Nature Commun. 10 (2019) 1894; [13] Y. Anraku et al, Nature Commun. 8 (2017) 1001.

52 4th CASNN Annual Meeting 2019

53 Abstracts of Invited Speakers

16:40-18:00 August 20th

54 Abstracts of Invited Speakers

08:00-12:20 August 21st

55 Abstracts of Invited Speakers

13:30-16:20 August 21st

Baran D. Sumer UT Southwestern Medical

Baran D. Sumer, MD, FACS is an Professor of Otolaryngology, Head and Neck Surgery at UT Southwestern Medical Center in Dallas Texas where he serves as the Chief of the Head and Neck Oncology Division in the Department of Otolaryngology. He also chairs the Head and Neck Cancer Disease Oriented Team at the Simmons Comprehensive Cancer Center. He received his B.A degree in Economics from Rutgers University in 1994 and obtained his M.D degree from Case Western Reserve University School of Medicine in May 2001. He completed post-graduate residency training as an intern in general surgery at Washington University School of Medicine Department of Surgery in Saint Louis, Missouri in 2002, and residency training in otolaryngology at Washington University, Department of Otolaryngology in 2006. Following completion of his otolaryngology residency, Dr. Sumer completed a Fellowship in Head and Neck Oncology, Transoral Laser Surgery, and Microvascular Reconstruction at Washington University, Department of Otolaryngology, Division of Head and Neck Surgery under Bruce H. Haughey, MBChB, MS, FACS, FRACS and Brian Nussenbaum, MD, FACS in August of 2007. His primary research interest is in the development of nanoparticles and nanodevices for surgical applications. One of the primary challenges during minimally invasive oncologic surgery is delineation of cancer from normal tissues especially in previously treated areas, and detection and destruction of residual microscopic disease. Recently in collaboration with Dr. Jinming Gao, Ph.D., Dr. Sumer established pH transistor nanoparticles (PTN) that in response to pH show binary off/on behavior, remaining completely dark until exposed to a specific tuned pH where they reach 100% fluorescence. The ultra-pH-sensitive property is a nanoscale phenomenon arising from the self- assembly of amphiphilic copolymers. Based on the sharp transition pH Dr’s Gao and Sumer established a nanoprobe to fluorescently image dysregulated pH, a universal hallmark of cancer. Critically, the binary all or nothing fluorescence, with no intermediate state, digitizes the analog biological signal, pH, allowing amplification without noise or distortion. These PTN have transformed tumor detection but also represent a new paradigm of digitizing an analog biologic signal with the exciting possibility other applications in tumor imaging, delivery of therapeutics and cellular targeting. Their work supported by the National Cancer Institute and NIH, as well as the Cancer Prevention Research Institute of Texas (CPRIT) and has transitioned to whole body imaging of cancers using positron emission tomography (PET). He serves as a reviewer for several peer-reviewed journals, including Nature Biomedical Engineering, Head and Neck, Laryngoscope, Experimental Biology and Medicine, International Journal of Otolaryngology, and Otolaryngology-Head and Neck Surgery. He is also an editor for the Annals of Surgical Oncology. Among numerous recognitions, honors, and awards, Dr. Sumer has been recognized as among the best otolaryngology physicians in North Texas by D Magazine. He is also the recipient of a Texas Instruments Corporate Award Research Gift, the Triological Society Francis Lederer FUSION Grant for Nanotechnology Research, and the SEBM Best Paper Award in the Alan MacDiarmid Interdisciplinary Research Society for Experimental Biology and Medicine. Dr. Sumer serves as principal investigator on several research projects funded by R01 and U01 awards from the National Institutes of Health (NIH) and the National Cancer Institute (NCI), and grants from the Cancer Prevention and Research Institute of Texas (CPRIT) and biotechnology companies including OncoNano Medicine.

4th CASNN Annual Meeting 2019

57 Targeting acidosis in cancer: a new strategy using a pH transistor nanoprobe for fluorescence-guided surgery in humans Sumer B.D*, Steinkamp P.J Voskuil F.J, van der Vegt B, Doff J.J, Zhao T, Hartung J, Jayalakshmi Y,Gao J, Witjes M.J.H, van Dam G.M Department of Otolaryngology Head and Neck Surgery, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America Introduction: Extracellular acidosis of the tumor environment is a universalphenomenon observed in solid tumors due to the Warburg Effect where tumor cells preferably convert glucose into lacticacid despite the presence of oxygen. Up to now, this hallmark of cancer has not been successfully exploited in diagnostic or therapeutic settings. ONM-100 is a polymer-based micellarimaging agent conjugated with ICG with an exquisitely pH-sensitive binary off/on mechanism that can be used for intra-operative tumor detection and margin assessment under clinically used near infrared cameras. Once accumulated in the tumor, the micelles dissociate in the acidic environments resulting in fluorescent activation of ICG. By targeting metabolic vulnerabilities of cancer with this unique pH- activatable approach, ONM-100 could overcome the limitations of other fluorescent imaging agents, such as antibody-dye conjugates which lack broad tumor applicabilitydue to biomarker-specific targeting. This first-in-human study investigates the safety and feasibility of ONM-100 as an intraoperative imaging agent for fluorescent imaging ofvarious solid tumors. Methods: In this phase I study, ONM-100 was IV administered 24±8h prior to surgery in a dose escalation scheme (0.1-1.2mg/kg)and the optimal dose was verified in a subsequent cohort with multiple solid tumors. Patients with histopathologicallyproven breast cancer (BC), head and neck squamous cell carcinoma (HNSCC), colorectal cancer (CRC) and esophageal cancer (EC) were included. Blood was drawn to assess safety and pharmacokinetic data. Intra-operative images were collected before and after tumor excision, from the surgical bed and of the specimen directly after excision using a standardized method. Fluorescence images were obtained from serially sliced specimens and formalin-fixated paraffin-embedded tissue blocks and correlated with standard histopathological assessment. Results: Thirty patients (11 BC, 13 HNSCC, 3 EC, 3 CRC) were enrolled. No treatment-related adverse events higher thanCTCAE grade 1, serious adverse events, or treatment-related aberrations in ECG, vital signs or laboratory were observed.Pharmacokinetic data showed a strong correlation between dose and exposure. A sharply demarcated fluorescent signal was observed in all 29 patients with viable tumor tissue with in vivo and/or ex vivo imaging (Figure 1), (median Tumor to Background Ratio 4.3; IQR 3.1) which correlated with tumor on final histopathology, irrespective of tumor type or ONM-100 dose. All tumor positive surgical margins in BC and HNSCC (N=9) and peritoneal metastasis could be detected by intra-operative fluorescence imaging. Conclusion: This study shows that ONM-100 is safe and allows universalfluorescent-based tumor visualization both in- and ex vivo in various solid tumors with high tumor to background fluorescence ratios and accurate histopathological correlations. These data suggest the potential clinical utility of ONM-100 inimproving the detection of positive margins and occult disease. References [1] Wang Y, Zhou K, Huang G, Hensley C, Huang X, et al. A nanoparticle-based strategy for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals. Nature Materials. 2014 Feb;13(2):204-12. [2] Zhou K, Liu H, Zhang S, Huang X, Wang Y, et al. Multicolored pH-tunable and activatable fluorescence nanoplatform responsive to physiologic pH stimuli. J Am Chem Soc. 2012 May 9;134(18):7803-11. [3] Li Y, Zhao T, Wang C, Lin Z, Huang G, et al. Molecular basis of cooperativity in pH-triggered supramolecular self-assembly. Nat Commun. 2016 Oct 27;7:13214. [4] Zhao T, Huang G, Li Y, Yang S, Ramezani S, et al. A Transistor-like pH Nanoprobe for Tumour Detection and Image-guided Surgery. Nat Biomed Eng. 2016;1

4th CASNN Annual Meeting 2019

Bing Xu Brandeis University

Dr. Bing Xu received his bachelor’s degree in 1987 and Master’s degree (Supervisor: Prof. Wenxia Tang) in 1990 from Nanjing University. He then obtained his Ph.D. in 1996 from the University of Pennsylavania (Supervisor: Prof. Timothy Swager). After a three-year postdoc at Harvard University, he started his independent career at the Department of Chemistry, Hong Kong University of Science and Technology University as an assistant professor in 2000. After rising to rank of full professor, he moved to Brandeis University in 2008. He was recognized as a highly cited researcher in the field of chemistry. His research interests focus on enzymatic noncovalent synthesis, self-assembly, hydrogels, cancer therapy, tissue engineering and gene therapy.

4th CASNN Annual Meeting 2019

59 Enzyme-Instructed self-assembly of peptide nanofibers Huaiming Wang, Zhaoqianqi Feng, Hongjian He, Jiaqing Wang, Bing Xu

Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454 Email: [email protected]

Introduction: Enzymatic reactions and self-assembly are two fundamental features of cells. Enzyme- instructed self-assembly (EISA), a process that integrates enzymatic reactions and supramolecular (i.e., noncovalent) interactions for generating molecular nanofibers, represents an emerging new approach for developing biomedical application of soft nanomaterials.[1] We choose to develop EISA for generating molecular nanofibers against drug resistance and immunosuppression. Methods: We designed, synthesized, and tested peptide molecules for mitochondrial EISA and use mitochondrial EISA for selectively delivering drugs into the mitochondria of cancer cells[2] for inhibiting drug resistant cancer cells in cell assays and examined cytoplasm EISA for inhibiting immunosuppressive tumors in a murine model. Results: Our studies have confirmed EISA to form nanofibers selectively on the mitochondria of cancer cells and EISA to deliver drugs into the mitochondria of drug-resistant cancer cells. In addition, we found that cytoplasm EISA inhibit an immunosuppressive osteosarcoma in a murine model.[3] Conclusion: The action EISA of peptide assemblies significantly departs from the ligand-receptor dogma of the current anticancer drugs. EISA ultimately may provide innovative anticancer approaches to address the problems of drug resistance and immunosuppression in cancer therapy.

Reference: [1] J. Zhou, B. Xu, Enzyme-instructed self-assembly: a multistep process for potential cancer therapy, Bioconjugate Chemistry, 26 (2015) 987-999. [2] H. He, J. Wang, H. Wang, N. Zhou, D. Yang, D.R. Green, B. Xu, Enzymatic Cleavage of Branched Peptides for Targeting Mitochondria, J. Am. Chem. Soc., 140 (2018) 1215-1218. [3] Z. Feng, X. Han, H. Wang, T. Tang, B. Xu, Enzyme-Instructed Peptide Assemblies Selectively Inhibit Bone Tumors, Chem, (2019) in press.

4th CASNN Annual Meeting 2019

Can Zhang China Pharmaceutical University

Dr. Can Zhang is the professor and Ph.D. supervisor in both medicinal chemistry and pharmaceutics. Now she is the dean of Institute of Pharmaceutical Sciences at China Pharmaceutical University and the associate editor of Biomaterials Science. Her research focused on the development of innovative biomaterials and nanomedicine. As principal investigator, she has completed more than 30 research projects at national, provincial and ministry level. She received the first prize for natural science by Ministry of Education and a third prize for progress in science and technology of Jiangsu Province. She was also awarded Young Scientist Award Nomination of Jiangsu Province, New Century Excellent Talents in University by Ministry of Education and “333 high-level talents training project” of Jiangsu Province. In recent years, she has published more than 100 papers, including Nat. Nanotech., Adv. Mater., J. Am. Chem. Soc. and Angew. Chem. Int. Ed. She was rated Chinese Highly-Cited Researchers in the recent six years (from 2013 to 2018).

4th CASNN Annual Meeting 2019

61 Living cyto-pharmaceuticals for tumor therapy Can Zhang

Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University 24 Tong Jia Xiang, Nanjing 210009, P. R. China Email: [email protected]

Nanomedicine has a great prospect in the treatment of tumor. However it cannot achieve a full therapeutic potential due to the existence of multiple physiological barriers on the transporting road to the lesions[1] . Our group proposed a novel, cyto-pharmaceutical strategy based on self-neutrophils to tackle the issues confronted by nanomedicine. Neutrophils, by responding to specific chemokines, can transmigrate multiple physiological barriers and penetrate into deep tumor, spontaneously. Therefore, cyto-pharmaceutical fabricated from neutrophils could enhance the tumor-targeting ability as well as therapeutic efficiency of chemotherapeutical drugs, thus expanding the anti-tumor indications. As a proof of concept, we first utilized surgery, radiotherapy or thermotherapy[1-3] to locally amplify the inflammatory signals in tumor, and then applied the cyto-pharmaceutical fabricated from self- neutrophils to treat tumors, synergistically. By taking advantage of the intrinsic properties of self- neutrophils, including responding to inflammatory chemokines, migrating across the physiological barriers and penetrating towards the deep tumor, the targeting efficiency of cyto-pharmaceutical was three order of magnitude higher than free drugs and one order of magnitude higher than drug-loaded liposomes, respectively. Cyto-pharmaceutical fabricated from self-neutrophils significantly inhibited the recurrence of tumor. Besides, the median survival period of mice receiving cyto-pharmaceutics could be extended to 2 months [1]. The personalized therapeutic regimen, which was combining cyto- pharmaceutical-mediated chemotherapy with surgery, radiotherapy or thermotherapy, could be further developed to treat other inflammation-related diseases.

Reference [1]. JW Xue, ZK Zhao, L Zhang, LJ Xue, SY Shen, YJ Wen, ZY Wei, L Wang, LY Kong, HB Sun, QN Ping, R Mo, C Zhang*. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence. Nature Nanotechnology, 2017, 12(7): 692-700. [2]. L Zhang, Y Zhang, YN Xue, Y Wu, QQ Wang, LJ Xue, ZG Su, C Zhang*. Transforming Weakness into Strength: Photothermal‐Therapy‐Induced Inflammation Enhanced Cytopharmaceutical Chemotherapy as a Combination Anticancer Treatment. Advanced Materials, 2019, 31(5): 1970033. [3]. CY Ju, YJ Wen, LP Zhang, QQ Wang, LJ Xue, J Shen, C Zhang*. Drug Delivery Vectors: Neoadjuvant Chemotherapy Based on Abraxane/Human Neutrophils Cytopharmaceuticals with Radiotherapy for Gastric Cancer. Small, 2019, 15(5): 1970028.

4th CASNN Annual Meeting 2019

Changyang Gong Sichuan University

Prof. Changyang Gong received his Ph.D. degree in cell biology from Sichuan University, Chengdu, China, under the guidance of Professor Yuquan Wei in 2010. He is currently a Professor of pharmaceutics at State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China. His current research focuses on novel drug and gene delivery system for tumor therapy, nanomedicine, and immune adjuvant for tumor vaccine. He has published more than 80 peer-review scientific papers in Adv Mater, ACS Nano, Adv Funct Mater, Biomaterials, etc. He is Editorial Board of Chinses Chemical Letters, BioMed Research International, etc. His scientific achievements have been honored by the National Science Fund for Excellent Young Scholars (2018), the National Program for Support of Top-notch Young Professionals (2014), Science & Technology Award for Young Talents of Sichuan University (2015), and Distinguished Young Scholars of Sichuan University (2015).

4th CASNN Annual Meeting 2019

63 Multifunctional bionic artificial virus delivers CRISPR/Cas9 system for cancer immunotherapy via targeting multiple immune checkpoints Ning Wang, Chao Liu, Wen Yang, Linjiang Song, Lu Li, Rui Luo, Chunqing Ou, Shuang Ma, Meiling Shen, Yuquan Wei, Qinjie Wu, Changyang Gong*

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China Email: [email protected]

Immune checkpoint blockade has shown the potential of triggering anti-tumor immune responses[1]. However, therapeutic effect of conventional single-target immune checkpoint blockade has been limited by the heterogeneity of tumors. Besides, owing to the large plasmid size and poor penetration in vivo, efficient delivery of CRISPR/Cas9 system into tumor cells still faces challenges[2-7]. In this work, a multifunctional bionic artificial virus containing a bioresponsive shell and high transfection efficiency core is designed to deliver novel multiple gene-targeting CRISPR/Cas9 system (MT-CRISPR/Cas9) in vivo. In addition, two immune checkpoints, PD-L1 and CD47, were used as model targets in the MT-CRISPR/Cas9 system for cancer immunotherapy. The high transfection efficiency of multifunctional bionic artificial virus with low vehicle/plasmid mass ratio (2:1) and excellent performance in serum highlights the latent capacity for its further application. Meanwhile, multifunctional bionic artificial virus induced higher gene editing efficacy of PD-L1 and CD47 than Lipofectamine 3000. After intravenous administration, the multifunctional bionic artificial virus with negative charged shell could achieve long-circulation and accumulate into tumor site. Followed by intelligent response to tumor microenvironment, the multifunctional bionic artificial virus changed to a smaller size with TAT-containing surface for facilitating tumor penetration and cellular uptake. Subsequently, the multifunctional bionic artificial virus could peel the shell into a positive charged and smaller core in lysosome, and then achieve effective disruptions of Pd-l1 and Cd47 synchronously in tumor cells by robust lysosome escape and fast nucleus localization. In vivo anti-tumor assay showed that multifunctional bionic artificial virus induced >90% regression of malignant melanoma and improved the overall survival of tumor-bearing mice with low side effects. In summary, the multifunctional bionic artificial virus pointed out a distinctive avenue for multiple targeting therapeutics and expanded the clinical applications of genome editing tools.

References [1] S.R. Gordon, R.L. Maute, B.W. Dulken, G. Hutter, B.M. George, M.N. McCracken, R. Gupta, J.M. Tsai, R. Sinha, D. Corey, A.M. Ring, A.J. Connolly, I.L. Weissman, PD-1 expression by tumour- associated macrophages inhibits phagocytosis and tumour immunity, Nature, 545 (2017) 495-499. [2] Y. Cheng, Fluorinated Polymers in Gene Delivery, ACTA POLYMERICA SINICA, 8 (2017) 1234-1245. [3] L. Li, L. Song, X. Liu, X. Yang, X. Li, T. He, N. Wang, S. Yang, C. Yu, T. Yin, Y. Wen, Z. He, X. Wei, W. Su, Q. Wu, S. Yao, C. Gong, Y. Wei, Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice, ACS Nano, 11 (2017) 95-111. [4] L. Li, L. Song, X. Yang, X. Li, Y. Wu, T. He, N. Wang, S. Yang, Y. Zeng, L. Yang, Q. Wu, Y. Wei, C. Gong, Multifunctional "core-shell" nanoparticles-based gene delivery for treatment of aggressive melanoma, Biomaterials, 111 (2016) 124-137. [5] H. Liu, Y. Wang, M. Wang, J. Xiao, Y. Cheng, Fluorinated poly(propylenimine) dendrimers as gene vectors, Biomaterials, 35 (2014) 5407-5413. [6] L. Li, X. Li, Y. Wu, L. Song, X. Yang, T. He, N. Wang, S. Yang, Y. Zeng, Q. Wu, Z. Qian, Y. Wei, C. Gong, Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy, Theranostics, 7 (2017) 1633-1649.

4th CASNN Annual Meeting 2019

Changyou Zhan Fudan University Department of Pharmacology, School of Basic Medical Sciences & State Key Laboratory of Molecular Engineering of Polymers

Dr. Changyou Zhan is a professor of pharmacology at School of Basic Medical Sciences, Fudan University. He obtianed his Ph.D. in Pharmarceutics from Fudan University in 2010. His recent research focuses on understanding the in vivo delivery mechanism of liposome-based targeting drug delivery systems. Dr. Zhan has published >70 peer-review scientific papers with citation by >2,800 times (H-index~29). His scientific achievements have been honored by scientific awards in China and the international, including, New Hundred-Talent Program of Shanghai Municipal Commission of Health and Family Planning (2018), Natural Science Award of Shanghai City (2016), Thousand- Talent Program for Young Outstanding Scientists of China (2015), Postdoctoral Fellow Award of American Association of Pharmaceutical Scientists (2013) and National Outstanding Doctoral Dissertation Award of China (2012).

4th CASNN Annual Meeting 2019

65 Protein corona on liposome-based nanomedicines Juan Guan1, Zui Zhang1, Tianhao Ding1, Jun Qian2, Changyou Zhan1,2,*

1 Department of Pharmacology, School of Basic Medical Sciences & State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200032, P.R. China 2 Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, P.R. China E-mail: [email protected]

Liposome-based nanomedicines have been extensively exploited for delivery of a variety of therapeutic agents. Many liposome-based nanomedicines have been approved for clinical treatments of cancers and infectious diseases. However, clinical translation of smart liposomes (such as active targeting and responsive liposomes) is extremely slow. None of such formulations have been approved so far for clinical use. Liposomes are surrounded by heavy plasma proteins after entry into blood stream, and the formation of protein corona on liposomal surface is believed to be a major causal factor for the unsuccessful clinical translation. Recently we find that natural IgM is a key plasma protein that reversely regulates in vivo performance of liposomes. After absorption on the liposomal surface, natural IgM efficiently activates complement, accelerating blood clearance and inducing enhanced immunogenicity. It becomes efficient to improve liposome formulations by reducing the natural IgM absorption. Furthermore, a bunch of ligand-targeted liposomes are prepared by conjugating different kinds of targeting ligands, including folic acid, RGD, CDX, A7R, Angiopep-2 peptides, and transferrin. Natural IgM absorption is ubiquitous on the surface of these ligand-targeted liposomes. It is interesting that the in vivo performances (such as pharmacokinetics, targeting yields, immunogenicity) of those liposomes reversely correlate with the absorbed amount of natural IgM in different species (mouse, rat and rabbit), suggesting natural IgM a potential biomarker for predicting in vivo performance of liposomes in preclinical screening. Our studies reveal the importance of natural IgM on regulating in vivo performances of liposomes, and provide new insights on optimization of liposomal formulations based on mechanistic understandings.

References [1] Ehrenstein, M. R.; Notley, C. A. Nat. Rev. Immunol. 2010, 10 (11), 778-86. [2] Allen, T. M.; Cullis, P. R. Adv. Drug Del. Rev. 2013, 65 (1), 36-48. [3] Guan, J.; Shen, Q.; Zhang, Z.; Jiang, Z.; Yang, Y.; Lou, M.; Qian, J.; Lu, W.; Zhan, C. Nat. Commun. 2018, 9 (1), 2982. [4] Vu, V. P.; Gifford, G. B.; Chen, F.; Benasutti, H.; Wang, G.; Groman, E. V.; Scheinman, R.; Saba, L.; Moghimi, S. M.; Simberg, D. Nat. Nanotech. 2019, 14, 260–8. [5] Guan, J.; Jiang, Z.; Wang, M.; Liu, Y.; Liu, J.; Yang, Y.; Ding, T.; Lu, W.; Gao, C.; Qian, J.; Zhan, C. Mol. Pharmaceut. 2019, 16 (2), 907-13.

4th CASNN Annual Meeting 2019

66 Prof. Chong Li

The Departments of pharmacy in Southwest University

He received BS degree from Sichuan University (China) in 2005, earned his Ph.D degree in pharmacy from the Fudan University in 2010. He is one of the young editorial board members in Acta Pharmaceutica Sinica B and Chinese Chemical Letters. Prof. Chong Li get several awards like the National "Top 100 Doctoral Thesis" (2013), 2nd Prize of Chinese Pharmaceutical Association for Science and Technology Awards (2014), Chinese Pharmaceutical Association – Zhongheng Youth Pharmacy Award (2015). Bayu Scholar of Chongqing (2015), and Chongqing Youth Talent Training Program (2015). His research interests focus on designing of functional peptide and its application in drug delivery.

4th CASNN Annual Meeting 2019

67 Overcoming the reticuloendothelial system barrier to drug delivery with a “Don’t-eat-us” strategy

Yixuan Tang, Xiaoyou Wang, Chong Li *

College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, P.R. China. Email: [email protected]

Overcoming the reticuloendothelial system (RES) has long been a vital challenge to nanoparticles as drug carriers. Modification of nanoparticles with polyethylene glycol helps them avoid clearance by macrophages, but also suppresses their internalization by target cells. To overcome this paradox, we developed an RES-specific blocking system utilizing a “don’t-eat-us” strategy. First, a CD47-derived, enzyme-resistant peptide ligand was designed and placed on liposomes (D-Self peptide-labeled liposome, DSL). After mainline administration, DSL was quickly adsorbed onto hepatic phagocyte membranes (including those of Kupffer cells and liver sinusoidal endothelial cells), forming a long- lasting mask that enclosed the cell membranes and thus reducing interactions between phagocytes and subsequently injected nanoparticles. Compared with blank conventional liposomes (CL), DSL blocked the RES at a much lower dose, and the effect was sustained for a much longer time, highly prolonging the elimination half-life of the subsequently injected nanoparticles. A brain-targeted peptide ligand on PLGA nanoparticles showed that brain accumulation of the drug was dramatically enhanced by this “don’t-eat-us” strategy, whereas a high-dose injection of CL reached the endothelium albeit with suppressed drug permeation through the blood-brain barrier. In conclusion, our study demonstrates a new strategy that blocks the RES by masking phagocyte surfaces to prolong nanoparticle circulation time without excess modification and illustrates its utility in enhancing nanoparticle delivery.

Scheme 1. Schematic diagram depicting enhanced delivery of nanoparticles by macrophage blockade. In this schematic illustration, DSL is first injected, and then the phagocytic activity of macrophages is inhibited by interactions between the D-Self peptide and SIRPα. In this way, DSL remains on the cell surface and masks macrophages for a prolonged period. Thus, the subsequently injected nanoparticles avoid clearance by macrophages and realize enhanced delivery efficiency to targeted organs.

References [1] R.K. Tsai, D.E. Discher, Inhibition of "self" engulfment through deactivation of myosin-II at the phagocytic synapse between human cells. J. Cell. Biol. 180(5) (2008) 989-1003. [2] A.N. Barclay, T.K. Van den Berg, The interaction between signal regulatory protein alpha (SIRPalpha) and CD47: structure, function, and therapeutic target. Annu. Rev. Immunol. 32 (2014) 25-50. [3] P.L. Rodriguez, T. Harada, D.A. Christian, D.A. Pantano, R.K. Tsai, D.E. Discher, Minimal "Self" peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science 339(6122) (2013) 971-975.

4th CASNN Annual Meeting 2019

68 Chuanlai Xu Jiangnan University

Prof. Chuanlai Xu received Beng (1987), MS (1990) and PhD (2002) degrees from Jiangnan University. He used to work as a visiting scholar at the University of East Anglia (2007) and University of Michigan (2008, Ann Arbor, Michigan), respectively. And now, his interests include combining the unique properties of nanoparticles with biological molecules (DNA, antigen and antibody), firstly proposed the quantitative determination based on plasmonic chirality. He realized single molecule detection in biological substrates and prepared serious detection probes such as immune-magnetic beads, fluorescence detection probes based on quantum dots, paper sensor based on carbon tubes. The biosensors above exhibit super sensitivity and good stability complex substrates. He has published more than two hundred and seventy (270+) peer reviewed journal articles. He won 4 second class of the state scientific and technological progress award (2007, 2009, 2011 and 2017). And he was elected to be the fellow of royal society of chemistry (FRSC, 2015) and selected for ten thousand talent project (2016).

4th CASNN Annual Meeting 2019

69 Constructing Chiral Probes for Biosensing and Bioimaging Liguang Xu, Maozhong Sun, Hua Kuang, Chuanlai Xu*

International Joint Research Laboratory for Biointerface and Biodetection; State Key Lab of Food Science and Technology, and School of Food Science and Technology, Jiangnan University, Wuxi, 214122, P.R.China * Corresponding author: [email protected]

Abstract: Well-defined chiral nanostructures assembled with discrete nanoparticles (NPs) have been used extensively as biosensors, for bioimaging, and for disease treatment because their morphological, optical, and physicochemical properties are both controllable and flexible. Using the various nanoscale building blocks, we concretely constructed diverse nanoparticle chiral assemblies for In vitro diagnostics, multimodal bio-imaging and phototherapy: DNA-frame driven plasmonic silver NPs self- assembled pyramids that enabled the simultaneous and ultrasensitive surface enhanced Raman scattering (SERS) detection of in vitro multiple quantitative disease biomarkers at the attomolar level. Furthermore, DNA-driven nanoparticle self-assembling pyramid encoding probes by containing a Raman reporter (Cy5) guaranteed the detection of telomerase in live cells using the bi-optical signals. And then, nanorod side-by-side dimers in living cells has been carried out successfully along with chiroplasmonic effects, SERS, and fluorescence properties, which was applied for in situ imaging and sensitive quantification of target miRNA through the CD signals and have the potential as the a quantitative platform for studying of biomolecular interactions, trafficking and kinetics in single living cells, as well as circular polarized light-induced phototherapy.

Keywords: Chirality, Self-assembly, DNA, Biosensors, Bio-imaging.

4th CASNN Annual Meeting 2019

Chuanliang Feng Shanghai Jiaotong University

Prof. Dr. Chuanliang Feng received Doctor Degree from University of Twente (the Netherlands) in 2005. After this, he was awarded Max-Planck Society Scholarship to work at Max-Planck Institute for Polymer Research in Mainz. From 1998 to July 2009, he was appointed as a research scientist in Biomade Technology Foundation (Groningen, the Netherlands). In Aug. 2009, he moved to Shanghai Jiaotong University as a full professor in School of Material Sciences and Technology. He was supported by Program for New Century Excellent Talents in University, Program for Shanghai Pujiang Excellent Talents, and Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. His research mainly focuses on Chiral biomaterials, polymeric materials, supramolecular hydrogels. Important topics are synthesis and characterization of chiral supramolecular hydrogels and biomimetic materials as well as applications of biomaterials in Regenerative Medicine. He has published more than 110 papers, including J. Am. Chem. Soc., Angew. Chem. Int. Ed., Adv. Mater. and so on. He has more than 20 patents. He is guest editor of European Polymer Journal, and editorial member of Advance Hybrid and Composite Materials. Recently, he has been awarded Richard Robert Ernst during PolyChar 2019 international conference due to his innovation contribution on supramolecular chemistry.

4th CASNN Annual Meeting 2019

71 The role of chiral molecules in helical nanofibers on cell adhesion Ting Peng, Jinying Liu, Chuanliang Feng*

State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China. E-mail: [email protected]

Introduction: Chirality is a fundamental property of nature, lucubrating of which leads researches to trace the origin of life. Recently, supramolecular chirality, regarded as chirality generated by molecular self- assembling through intermolecular noncovalent interactions, has attracted greater attention, since it plays critical role in various areas, eg. drug delivery and cell culture. The regulation of supramolecular chirality are been mainly achieved by changing intrinsic molecular structure and external factors. However, these regulation methods come along with many problems such as poor biocompatibility, structural instability and operational difficulties. Furthermore, the influence of chiral molecules on cells behavior in systems involving both supramolecular and molecular chirality is unclarified. To address this issue, supramolecular hydrogel fabricated based on homochiral L-phenylalanine derivative with good biocompatibility is obtained, the supramolecular chirality of it can be simply inverted between P and M through odd−even effect by varying the number of -CH2- and -NH- units between the chiral center and rigid aromatic core of the C2-symmetric hydrogelators.[1] The thus obtained supramolecular hydrogels with good biocompatibility and stable structure provide a more rigorous strategy of investigating the effects of supramolecular chirality on cell behaviors while that of molecules chirality is circumvented. This study paves a way to design biocompatible system with controllable supramolecular chirality and explore the origin of life.

Figure 1. a) Molecular structures of gelators BA, BE and BP derived from L-phenylalanine derivative, and schematic illustration of helical chirality inversion tuned by the variable methylene units number n from 0 to 2; b) CD spectra of chiral gelators and their assembled nanofibers; c) SEM images of right/ left-handed helical fibers in the BA,BP/ BE xerogel respectively; d) Fluorescence microscopy images of Hy926 cells in BA, BE and BP hydrogels after culture for 5 days, respectively, the enhanced cell proliferation in BA hydrogels with left-handed nanofibers was proved

References: [1] J. Y. Liu, X. Y. Ma, C. L. Feng, The Cooperative Effect of both Molecular Chirality and Supramolecular Chirality on Cell Adhesion, Angew. Chem. Int. Ed. 57(2018), 6475-6479

4th CASNN Annual Meeting 2019

72 Chun Wang University of Minnesota Twin Cities

Dr. Chun Wang received his Ph.D. in Bioengineering under Jindřich Kopeček at the University of Utah in 2001. He was an NIH postdoctoral fellow with Robert Langer at Massachusetts Institute of Technology. Currently he is an Associate Professor and Director of Undergraduate Studies in the Department of Biomedical Engineering, University of Minnesota. He was a recipient of the National Science Foundation CAREER Award, Wallace H. Coulter Foundation Early Career Translational Research Award, and McKnight Land-Grant Professorship. He served on the editorial boards of the Journal of Controlled Release (2006-2016) and Advanced Drug Delivery Reviews (since 2010). He has published 80 peer-reviewed research articles and reviews and has given over 110 invited talks. His research interest is in polymer-based therapeutic biomaterials with applications in controlled drug delivery, immunotherapy, medical devices, and regenerative medicine.

4th CASNN Annual Meeting 2019

73 Liquid Polymer Matrices (LPMs) for Delivering Cancer Immunotherapy Chun Wang

4th CASNN Annual Meeting 2019

Chunying Chen National Center for Nanoscience and Technology

Prof. Chunying Chen is a principal investigator at National Center for Nanoscience and Technology of China. She received her Bachelor's degree in Chemistry (1991) and PhD degree in Biomedical Engineering (1996) from Huazhong University of Science and Technology of China. Her research interests include the potential toxicity of nanoparticles, therapies for malignant tumors using theranostic nanomedicine systems and vaccine nanoadjuvants using nanomaterials, which are supported by the China MOST 973 Program, NSFC, EU-FP6 and FP7 and IAEA. She has authored/co-authored over 150 peer-reviewed papers, 5 books and 10 book chapters. She has been awarded the second prize of the National Natural Science Award (2018, 2012), Outstanding Female Awards of the Chinese Academy of Sciences (2017), National Science Fund for Distinguished Young Scholars (2014), Chinese Outstanding Young Female Scientists Awards (2014). She serves as Editor- in-Chief for NanoImpact and an Associate Editor for Science Bulletin, Nanoscale, Nanoscale Advances, etc.

4th CASNN Annual Meeting 2019

75 Roles of the Protein Corona in Nanomedicine Chunying Chen

4th CASNN Annual Meeting 2019

Daishun Ling Zhejiang University

Daishun Ling, Principal investigator and Professor of the College of Pharmaceutical Science, Zhejiang University. Prof. Daishun Ling received his Ph.D. (2013) in School of Chemical and Biological Engineering from Seoul National University. Later, he worked as a senior researcher at the Center for Nanoparticle Research, Institute for Basic Science. Since joined the faculty of College of Pharmaceutical Sciences at Zhejiang University in 2014 through “Zhejiang University 100 Talent Professor”, he has been focusing on the dynamic assembly/disassembly of functional nanoparticles, stimuli-responsive nanomedicines, designed synthesis and surface engineering of functional nanomaterials for biomedical applications. Up to now, he has published > 70 papers in prominent international journals such as Nat. Mater., Nat. Biomed. Eng., J. Am. Chem. Soc., Angew. Chem. Int. Ed., Adv. Mater., ACS Nano, Adv. Funct. Mater., Nano Lett., ACS Cent. Sci., Biomaterials, Small, etc. He has been serving as Board Member of Science Bulletin, Youth Editorial Board Member of Acta Pharm. Sin. B and Chinese Chem. Lett.. He has received several prestigious fellowships and awards including the National 1000 Plan for Young Talents, the National Science Found for Excellent Youth Scholars, and the National Key Research and Development Program for Young Scientist

4th CASNN Annual Meeting 2019

77 Dynamic superparticles for biomedical applications Daishun Linga,b,c,* a College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China b Key Laboratory of Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310058, China c Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, China Email: [email protected]

Nanotechnology has received significant attention recently because of its important role in biomedical research. The materials consisting of the nanoparticles produce fascinating and various functionalities [1-3]. The controllable assembly mediated by a multitude of smart ligands would lead to the flexible modulation of nanomaterials’ fate in vivo [4-7]. The clever fabrication of dynamic superparticles via the ligands directed nanoparticle self-assemblies would lead to developing multifunctional nano-biomedical platforms for simultaneous targeted delivery, fast diagnosis, and efficient therapy [8,9]. Furthermore, the ingenious control over the assembly/disassembly process based on small-sized inorganic nanoparticles could achieve both in vivo targeted delivery and subsequent excretion caused by environmental stimuli-responsive disassembly [10].

References [1] Q. Weng, X. Hu, J. Zheng, F. Xia, N. Wang, H. Liao, Y. Liu, D. Kim, J. Liu, F. Li, Q. He, B. Yang, C. Chen, T. Hyeon, D. Ling, Toxicological risk assessments of iron oxide nanocluster- and gadolinium- based T1MRI contrast agents in renal failure rats, ACS Nano 13 (2019) 6801-6812. [2] H. Wu, F. Li, W. Shao, J. Gao, D. Ling, Promoting angiogenesis in oxidative diabetic wound microenvironment using a nanozyme-reinforced self-protecting hydrogel, ACS Cent. Sci. 5 (2019) 477-485. [3] Q. Chen, Y. Du, K. Zhang, Z. Liang, J. Li, H. Yu, R. Ren, J. Feng, Z. Jin, F. Li, J. Sun, M. Zhou, Q. He, X. Sun, H. Zhang, M. Tian, D. Ling, Tau-targeted multifunctional nanocomposite for combinational therapy of Alzheimer's disease, ACS Nano 12 (2018) 1321-1338. [4] F. Li, Z. Liang, J. Liu, J. Sun, X. Hu, M. Zhao, J. Liu, R. Bai, D. Kim, X. Sun, T. Hyeon, D. Ling, Dynamically reversible iron oxide nanoparticle assemblies for targeted amplification of T1- weighted magnetic resonance imaging of tumors, Nano Lett. (2019) DOI: 10.1021/acs.nanolett.8b04411. [5] F. Li, Y. Du, J. Liu, H. Sun, J. Wang, R. Li, D. Kim, T. Hyeon, D. Ling, Responsive assembly of upconversion nanoparticles for pH-activated and near-infrared-triggered photodynamic therapy of deep tumors, Adv. Mater. 30 (2018) 1802808. [6] J. Lu, J. Sun, F. Li, J. Wang, J. Liu, D. Kim, C. Fan, T. Hyeon, D. Ling, Highly sensitive diagnosis of small hepatocellular carcinoma using pH-responsive iron oxide nanocluster assemblies, J. Am. Chem. Soc. 140 (2018) 10071-10074. [7] F. Li, J. Lu, X. Kong, T. Hyeon, D. Ling, Dynamic nanoparticle assemblies for biomedical applications, Adv. Mater. 29 (2017) 1605897. [8] T. Zhang, F. Li, Q. Xu, Q. Wang, X. Jiang, Z. Liang, H. Liao, X. Kong, J. Liu, H. Wu, D. Zhang, C. An, L. Dong, Y. Lu, H. Cao, D. Kim, J. Sun, T. Hyeon, J. Gao, D. Ling, Ferrimagnetic nanochains-based mesenchymal stem cell engineering for highly efficient post-stroke recovery, Adv. Funct. Mater. 29 (2019) 1900603. [9] J. Wu, F. Li, X. Hu, J. Lu, X. Sun, J. Gao, D. Ling, Responsive assembly of silver nanoclusters with a biofilm locally amplified bactericidal effect to enhance treatments against multi-drug- resistant bacterial infections, ACS Cent. Sci. (2019) DOI: 10.1021/acscentsci.9b00359. [10] X. Hu, J. Sun, F. Li, R. Li, J. Wu, J. He, N. Wang, J. Liu, S. Wang, F. Zhou, X. Sun, D. Kim, T. Hyeon, D. Ling, Renal-clearable hollow bismuth subcarbonate nanotubes for tumor targeted computed tomography imaging and chemoradiotherapy, Nano Lett. 18 (2018) 1196-1204.

4th CASNN Annual Meeting 2019

78 Dan Ding Nankai University

Prof. Dan Ding received his PhD degree in Polymer Chemistry and Physics from Nanjing University in 2010. After a postdoctoral training in the National University of Singapore, he joined Nankai University in March 2013, where he is currently a professor in the College of Life Sciences and State Key Laboratory of Medicinal Chemical Biology. He also conducted his work in The Hong Kong University of Science and Technology as a visiting scholar. In 2013, he was selected in the Tianjin 1,000 Young Talents Plan. In 2014, he was also selected in the 100 Young Academic Leaders Plan in Nankai University. In 2016, he was obtained the China National Science Fund for Outstanding Young Researchers. His current research interest focuses on the design and preparation of nanomedicines and new molecular imaging probes as well as exploration of their biomedical applications. His research group is utilizing semiconducting conjugated polymers, fluorogens with aggregation-induced emission (AIE) characteristics, or environment-sensitive fluorophores to fabricate the molecular imaging probes.

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79 Afterglow luminescent AIE dots for biomedical applications Dan Ding

College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China Email: [email protected]

In recent years, aggregation-induced emission luminogens (AIEgens) have been emerged as promising fluorescent materials for versatile biomedical applications due to their unique merits in terms of opposed aggregation-caused quenching (ACQ) effect, high fluorescence in aggregated state, excellent photostability, unique restriction of intramolecular motion mechanism, as well as negligible cytotoxicity and in vivo toxicity. On the other hand, afterglow luminescent organic/polymeric materials have received increasing attention, as they can luminesce for a long time after a short-time light excitation, thus achieving improved sensitivity, enhanced tissue penetration, and minimized tissue autofluorescence. In this study, we aim to integrate both the advantages of AIEgens and afterglow luminescent materials by design and synthesis of afterglow luminescent AIE nanoparticles (termed afterglow luminescent AIE dots). By rational design, the resultant afterglow luminescent AIE dots with hydrodynamic diameters of around 120 nm can emit luminescence more than 1 day after single white light excitation for 5 min. The luminescence that the afterglow luminescent AIE dots emit has a peak centered at 670 nm and possess a big emission tail above 800 nm. It is found that the afterglow luminescent AIE dots are capable of penetrating tissue for about 1 cm. The afterglow luminescent AIE dots were then applied for tumor detection in vivo. 4T1 breast cancer cells were used to establish the tumor-bearing mouse model. After injection of afterglow luminescent AIE dots into 4T1 tumor-bearing mice, the dots are enriched in the tumor mass by EPR effect. As the lifetime of mouse autofluorescence is at nanosecond level, it is facile to differentiate the long-lasting afterglow luminescence from the mouse autofluorescence. Therefore, the tumor tissues are able to be detect in a rather high-contrast manner. It is also found that the emission of afterglow luminescent AIE dots can be easily quenched in the normal tissues, such as liver and spleen. As the nanomaterials are prone to accumulation in these organs, as compared to currently available fluorescent nanoparticles and afterglow luminescent nanoparticles, high tumor-to-normal organ signal ratios are realized. The afterglow luminescent AIE dots were then applied for image-guided cancer surgery. Thanks to the long-lasting afterglow luminescence, the afterglow luminescent AIE dots can help the surgeon detect the micro-sized tumors and residue tumors during the surgery. Furthermore, the afterglow luminescent AIE dots are also able to differentiate tumor and inflammation in vivo owing to the different pH values in these two tissues. The afterglow luminescent AIE dots will open up a new door to develop advanced bioprobes for disease diagnosis [1-3].

References [1] X. Ni, X. Zhang, X. Duan, H. L. Zheng, X. S. Xue, D. Ding, Near-infrared afterglow luminescent aggregation-induced emission dots with ultrahigh tumor-to-liver signal ratio for promoted image- guided cancer surgery, Nano Lett. 19 (2019) 318–330. [2] C. Chen, H. Ou, R. Liu, D. Ding, Regulating the photophysical property of organic/polymer optical agents for promoted cancer phototheranostics, Adv. Mater. 31(2019) 1806331. [3] J. Qi, C. Chen, X. Zhang, X. Hu, S. Ji, R. T. K. Kwok, J. W. Y. Lam, D. Ding, B. Z. Tang, Light- driven transformable optical agent with adaptive functions for boosting cancer surgery outcomes, Nat. Commun. 9(2018) 1848.

4th CASNN Annual Meeting 2019

80 David Tai Leong National University of Singapore

Dr. David Tai Leong is an Associate Professor at the Department of Chemical and Biomolecular Engineering, National University of Singapore (NUS). He obtained his PhD in Biology and Bachelor in Chemical Engineering from NUS and was trained in Howard Hughes Medical Institute at the University of Pennsylvania as a postdoc fellow. He was a recipient of the prestigious Lee Kuan Yew Fellowship and recently elected into the Royal Society of Chemistry as a Fellow. His research interests span across fundamental understanding of biological effects of nanomaterials to their applications. He has published over 130 publications over his scientific career, in top journals like Nature Nanotechnology, Nature Communications, Chemical Society Reviews, ACS Nano, Nano Letters, Advanced Functional Materials, JACS, Angewandte Chemie, NPG Asia Materials, Advanced Drug Delivery Reviews and Biomaterials. He has a h-index of 50 with total citations of more than 7800.

4th CASNN Annual Meeting 2019

81 Engineering Endothelial Leakiness With Nanoparticles David Tai Leong

Many nanomedicine and nano drug carrier systems depend on the tumor derived enhanced permeability and retention effect (EPR). However, the EPR effect and leaky vessels network within and along the periphery of the tumor is un-engineerable as it is entirely due to the tumor’s own metabolic demands and induction. This talk will share our discovery that nanoparticles themselves are capable of inducing endothelial leakiness and coined this phenomenon as “nanomaterials induced endothelial leakiness” (NanoEL)1. The gaps that are formed between endothelial cells are so large that whole cancer cells are able to migrate across them1,2. In one form of NanoEL, we showed that certain types of nanoparticles find their way between the endothelial cells and bind to an important adherens junction protein (VE-cadherin) and disrupt the adherens junction. This disruption then triggers an intracellular pathway that pulls adjacent endothelial cells to form those NanoEL gaps. NanoEL happens even without any cancer cells. Size3, charge4 and materials’ effective density5 determine NanoEL. While NanoEL poses a certain level of nanosafety risk6, engineering NanoEL7,8 can also have therapeutic outcomes like independently tuning leakiness7 for nanomedicine or drug access to cancer cells8. This talk will also introduce a new paradigm of classifying nanomaterials induced endothelial leakiness9 into Type I (Direct) and Type II (Indirect) NanoEL. I will also share some of our latest work on transition metals dichalcogenides10 and cell membrane nanotechnology11.

References 1. Setyawati, Nat Comms 2013, 4, 1673. 2. Peng, Nat Nanotech 2019, 14, 278 3. Setyawati, ACS Nano 2017, 11, 5020. 4. Wang, Chem Mat. 2018, 30, 3759. 5. Tay, ACS Nano 2017, 11, 2764. 6. Setyawati, Chem Soc Rev 2015, 44, 8174. 7. Tee, Nanotoxicology 2019. DOI: 10.1080/17435390.2019.1571646. 8. Setyawati, ACS Nano 2016, 10, 1170. 9. Tee, Chem Soc Rev 2019 (under revision)

4th CASNN Annual Meeting 2019

Dongsheng Guo Nankai University

Dongsheng Guo obtained his Ph.D degree at Nankai University (Supervisor: Prof. Yu Liu) in 2006. Then he joined Prof. Yu Liu’s group as a faculty member at College of Chemistry, Nankai University. He was promoted as an associate professor in 2008, and a full professor in 2013. During Sep.-Nov. 2014, he has been a DAAD fellowship at Jacobs University Bremen, Germany. Since 2014, he began to work independently as a principle investigator at Nankai University. The current research interest in his group is supramolecular biomedical materials based on calixarenes. He has published over 100 publications over his scientific career, in top journals like Nat. Chem., Adv. Mater., J. Am. Chem. Soc., Angew. Chem. Int. Ed., Acc. Chem. Res., Chem. Soc. Rev. He has a h-index of 35 with total citations of more than 3500.

4th CASNN Annual Meeting 2019

83 Tumor-responsive host-guest complexation: a supramolecular phototheranostics strategy Xin-Yue Hu, Dong-Sheng Guo*

College of Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China. E-mail: [email protected]

Supramolecular chemistry has been tightly connected to life science since its invention, and a lot of research topics, including supramolecular biomedical materials,1 supramolecular medicine,2 supramolecular chemotherapy,3,4 supramolecular phototheranostics,5 have sprung out in this interdisciplinary field. Our group focuses on supramolecular biomedical materials based on calixarenes. We proposed a host-guest strategy called biomarker displacement activation (BDA) by using GC5A-12C as a nanocarrier (Scheme 1).6 GC5A-12C annihilated the fluorescence and photoactivity of the photosensitizer (PS), but these properties would be recovered after ATP, which is overexpressed in tumor tissue, displacing PS. This BDA strategy achieves supramolecular phototheranostics that both visualize tumors in real time and ablate cancer efficiently. Another system which response to hypoxia was constructed by CAC4A (Scheme 1) and dye.7 The azo groups were reduced by hypoxia, resulting in the release of dye. This system was used to image the hypoxia in cancer cells successfully.

Scheme 1. Schematic illustration of a) the GC5A-12C nanocarrier for BDA, b) host-guest system based on CAC4A for hypoxia imaging.

References [1] M. J. Webber, R. Langer, Drug delivery by supramolecular design, Chem. Soc. Rev. 46 (2017) 6600−6620. [2] Q. Sun, Z. Zhou, N. Qiu, Y. Shen, Rational design of cancer nanomedicine: nanoproperty integration and synchronization, Adv. Mater. 29 (2017) 1606628. [3] H. Chen, Y. Chen, H. Wu, J.-F. Xu, Z. Sun, X. Zhang, Supramolecular polymeric chemotherapy based on cucurbit[7]uril-PEG copolymer, Biomaterials 178 (2018) 697−705. [4] J. Zhou, G. Yu, F. Huang, Supramolecular chemotherapy based on host-guest molecular recognition: a novel strategy in the battle against cancer with a bright future, Chem. Soc. Rev. 46 (2017) 7021−7053. [5] G. Yu, X. Chen, Host-guest chemistry in supramolecular theranostics, Theranostics 11 (2019) 3041−3074. [6] J. Gao, J. Li, W.-C. Geng, F.-Y. Chen, X. Duan, Z. Zheng, D. Ding, D.-S. Guo, Biomarker displacement activation: a general host-guest strategy for targeted phototheranostics in vivo, J. Am. Chem. Soc. 140 (2018) 4945−4953. [7] W.-C. Geng, S. Jia, Z. Zheng, Z. Li, D. Ding, D.-S. Guo, A noncovalent fluorescence turn-on strategy for hypoxia imaging, Angew. Chem. Int. Ed. 58 (2019) 2377−2381.

4th CASNN Annual Meeting 2019

84 Fang Yang Southeast University (China)

Fang Yang is a Professor at the School of Biological Sciences & Medical Engineering in Southeast University. She obtained her PhD in Biomedical Engineering from Southeast University in 2009. She was a visiting scholar at the University of Michigan, and at the University of California, Davis in 2012, and in 2014, respectively. Her research interests mainly focus on multi-functional theranostic drug delivery systems, microbubble-assisted ultrasound contrast imaging, ultrasound multimodal imaging and therapy. She has published more than 60 articles including Adv. Mater., ACS Nano, Adv. Funct. Mater., Theranostics, Small, Biomaterial, J. Control. Release, etc. One chapter for an English academic book and two chapters academic books in Chinese. As the participant, she has winned the first prize of the Natural Science of the Ministry of Education (ranked 3/8 in 2018), the gold medal with the congratulations of the Jury in the 46th Geneva International Invention Exhibition (ranked 2/5 in 2018), National Excellent Doctoral Dissertation of China (2011), first prize of Jiangsu Science and Technology Award (ranked 5/11 in 2018), Jiangsu Province Medical Science and Technology Third Prize (ranked 2/5 in 2014).

4th CASNN Annual Meeting 2019

85 Magneto-Acoustic Responsive Bubble Drug Delivery Fang Yang

4th CASNN Annual Meeting 2019

Gang Liu Xiamen University

Gang Liu received his M.D. degree from North Sichuan Medical College (China) in 2002 and Ph.D. degree from Sichuan University (China) in 2009. Subsequently, He focused his training on nanomedicine and molecular imaging at the National Institutes of Biomedical Imaging and Bioengineering, National Institutes of Health. In 2012, he joined the Center for Molecular Imaging and Translational Medicine, Xiamen University. Currently he is a Full Professor of Biomedical and Bioengineering and his research interests include biomaterials, theranostics, and molecular imaging. Dr. Liu has published more than 180 peer-reviewed papers, including more than twenty ESI highly cited papers (total citation >5,000 times). He has also published 4 books and 12 book chapters, and holds more than 10 patents at present.

4th CASNN Annual Meeting 2019

87 Re-engineering nanovesicles as a versatile drug delivery system for cancer therapy Gang Liu

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, China. Email: [email protected]

The development of smart nanoparticles that enable to circumvent biological barriers and transport cargoes to target sites in the body promises safer and more effective drug delivery. Since cell membrane-based nanovesicles have the characteristics of both nano-sized and cell-based drug delivery platforms, they are regarded as promising cancer targeted delivery tools for both endogenous and exogenous cargos. What is perhaps most fascinating about these cell membrane-based drug delivery systems is that the natural targeting ability of those producing cells makes the exogenous engineering of targeting moieties unnecessary. In our laboratory, a variety of bio-inspired nano-biomaterials, such as virus-like nanoparticles and ferritin nanocages, have been studied for drug delivery, cell labeling, and gene therapy. A number of hybrid nanoparticles containing synthetic and biological components have been utilized for achieving sustained release and target-specific delivery. We are particularly interested in cell membrane-based nanoparticles containing bioactive molecules useful for therapeutic and imaging applications in cancer theranostics. In this presentation, an innovative biomimetic nanoparticle platform for delivering therapeutic anticancer agents and imaging-guided cancer therapy will be introduced. In addition, the major hurdles in the clinical translation of cell membrane-based delivery systems will be discussed.

4th CASNN Annual Meeting 2019

Gang Zheng University of Toronto

Dr. Gang Zheng is a Professor of Medical Biophysics and Canada Research Chair in Cancer Nanomedicine at the University of Toronto. He is also the Associate Research Director of the Princess Margaret Cancer Center. Dr. Zheng received his B.Sc. in Chemistry from the Hangzhou University (now Zhejiang University) in 1988 and Ph.D. in Medicinal Chemistry from the SUNY Buffalo in 1999. Following a postdoctoral training in photodynamic therapy at the Roswell Park Cancer Institute, he joined the University of Pennsylvania in 2001 as an Assistant Professor of Radiology and moved to Canada in 2006. His lab is most well-known for the development of activatable photosensitizers for photodynamic therapy and the discovery of porphysome nanotechnology in cancer imaging and therapy. Dr. Zheng is a Fellow of the American Institute of Medical and Biological Engineering and an Associate Editor for the Bioconjugate Chemistry.

4th CASNN Annual Meeting 2019

89 Porphyrin nanomedicine: from fundamentals to applications Gang Zheng

Princess Margaret Cancer Centre; Department of Medical Biophysics, University of Toronto, 101 College Street, PMCRT 5-354, Toronto, ON M5G 1L7, Canada Email: [email protected]

Porphyrins are aromatic, organic, light-absorbing molecules that occur abundantly in nature, especially in the form of molecular self-assemblies. By conjugating porphyrins to lipids, we formed porphysomes,[1] self-assembled liposome-like nanoparticles with intrinsic multimodal photonic properties. High-density porphyrin packing in the nanoparticle bilayer enables light absorption and conversion to heat with extremely high efficiency, making porphysomes ideal candidates for photothermal therapy and photoacoustic imaging. Upon nanostructure dissociation during cell uptake, the fluorescence and photodynamic activity of the porphyrin monomers is restored. In addition, metal ions can be directly incorporated into the porphyrin building blocks of the preformed porphysomes, thus unlocking their potential for PET and MRI. By changing the way porphyrin-lipids assemble, we developed lipoprotein-like porphyrin nanoparticles,[2] porphyrin microbubbles, porphyrin nanodroplets, hybrid porphyrin-metal nanoparticles, and metal-chelating nanotexaphyrins,[3] thus expanding the purview of porphyrin nanomedicine. By mimicking the light harvesting systems found in photosynthetic bacteria, we have created supramolecular assemblies of highly ordered porphyrin aggregates possessing stimuli-responsive photonic properties (e.g., reversible/tunable photoacoustic sensing and self-regulating phototherapy).[4] Such optical properties are also responsible for our discovery of the ultrasound-induced microbubbles-to-nanoparticle conversion phenomenon,[5] which may open the door to EPR-adaptive nanomedicine delivery to tumors. We have now validated porphysome’s multimodal utilities in different cancer types, tumor models, and animal species. The effort of moving porphysomes towards first-in-human use is well on its way. In summary, the simple yet intrinsic multimodal nature of porphyrin nanomedicine represents a new nanomedicine paradigm[6] and also confers high clinical translation potential.

References [1] J.F. Lovell, C.S. Jin, E. Huynh, H.L. Jin, C.H. Kim, J.L. Rubinstein, W.C.W. Chan, W.G. Cao, L.H.V.Wang, G. Zheng, Porphysome Nanovesicles Generated by Porphyrin Bilayers for use as multimodal biophotonic contrast agents, Nature Materials 10 (2011) 324-332. [2] N. Muhanna, L.Y. Cui, H. Chan, L. Burgess, C.S. Jin, E. Huynh, F. Wang, J. Chen, J.C. Irish, G. Zheng,Multimodal Image-Guided Surgical and Photodynamic Interventions in Head-and-Neck Cancer: From Primary Tumor to Metastatic Drainage, Clinical Cancer Res. 22 (2016) 961-970. [3] J.M. Keca, J. Chen, M. Overchuk, N. Muhanna, C.M. MacLaughlin, C.S. Jin, W.D. Foltz, J.C. Irish, G Zheng, Nanotexaphyrin: One-Pot Synthesis of a Manganese Texaphyrin-Phospholipid Nanoparticle for Magnetic Resonance Imaging, Angewandte Chemie 55 (2016), 6187-91. [4] K.K. Ng, R. Weersink, S.L. Lim, B.C. Wilson, G. Zheng G, Controlling spatial heat and light distribution using photothermal enhancing auto-regulated liposomes (PEARL), Angewandte Chemie 55 (2016), 10003-7. [5] E. Huynh, B.L. Helfield, B.Y.C. Leung, M. Shakiba, J.A. Gandier, C.S. Jin, E.R. Master, B.C. Wilson, D.E. Goertz, G Zheng, In Situ Conversion of Porphyrin Microbubbles to Nanoparticles for Multimodality Imaging, Nature Nanotechnology 10 (2015) 325-332. [6] E. Huynh, G. Zheng, Engineering Multifunctional Nanoparticles: All-in-One Versus One-for-All, Wiley Nanomedicine & Nanotechnology 5 (2013) 250-65.

4th CASNN Annual Meeting 2019

Prof. Guanghui Ma

Institute of Process Engineering, Chinese Academy of Sciences

Prof. Guanghui Ma graduated from Gunma University, Japan (1988) as a scholarship student of China Education Ministry, and received her Ph.D. (1993) in Polymer Chemistry from Tokyo Institute of Technology. She started his academic career at Tokyo University of Agriculture and Technology as Assistant Professor (1994). She moved to Institute of Process Engineering, Chinese Academy of Sciences as a full professor (2001), and was appointed as Vice Director of State key Laboratory of Biochemical Engineering (2002), Vice Director of Institute of Process Engineering (2005). She has been appointed as Director of State key Laboratory of Biochemica Engineering since 2012. Prof. Ma is one of the earliest women scientists who have won the China National Science Fund for Distinguished Young Scholars. She has been engaged in the area of functional nano-microparticles for systematic theoretic study and innovative biomedical applications. For example, 1) She established the Membrane Emulsification Technique to prepare uniform sized nano-microspheres; 2) She discovered a variety of new merits of polysaccharides particles including the autofluorescence property, environmental sensitive response; 3) She established large-scale preparation platform of uniform nano-microparticles, which have been successfully designed for bio-separation media, drug release carrier and particle adjuvant.

Prof. Ma has published 382 papers (192 first/corresponding author), such as Nature Materials, Nature Commun, JACS, Adv Materials, ACS Nano, Biomaterials. She edited/wrote 12 books, such as "Microspheres and Microcapsules in Biotechnology". She is also an invited editor for special issue of Small, Vaccine, etc. She has been authorized 92 patents, some of them have been transferred to companies and developed to a series of commercialized products.

She has received Outstanding Contribution Award from federation of Biotechnology (AFOB), the First Prize of Beijing Science and Technology Award, and the Second Prize of National Technological Invention Award, TWAS-TWOWS-SCOUPS Regional Young Women Researcher Award, and so forth.

4th CASNN Annual Meeting 2019

91 Bridging systemic and gastrointestinal immune responses for enhanced vaccinations Guanghui Ma*, Yufei Xia, Jie Wu

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China E-mail: [email protected]

Gastrointestinal immune response is important for gastrointestinal infections such like Hand- Foot-Mouth disease. However, as peripheral lymphocytes are typically excluded from the gastrointestinal lymph tissues, current parenteral vaccinations failed to simultaneously induce systemic and mucosal responses. To break the natural barrier, we developed and heralded “immunoticket” capsules. By utilizing internal phase separation, the microcapsule was formed with positive charged shells and oily core (oil-in-polymer particles) to spatiotemporally deliver antigens and all-trans retinoic acid (RA). After intramuscular vaccinations, these capsules functioned as immunoticket to cultivate the peripheral DCs with chemokine receptor 9 (CCR9). By hitchhiking on the concentration gradient of chemokine (C-C motif) ligand 25 (CCL25), the primed DCs would home to the gut associated lymphoid tissues (GALTs) and induced antigen-specific IgA secretion and T cell engagements. Compared with the currently employed RA-involved formulations, the immunoticket capsules stimulated enhanced RA-mediated gut-tropism by mounting the inflammatory innate immunity. By controlling RA payloads, the potential regulatory T cell engagement was circumvented. In OVA and EV71 vaccinations, the immunoticket capsules induced potent serum IgG titer, antigen- specific cytotoxic T cells in the peripheral lymph tissues, as well as robust IgA secretion and T cell engagements on gastrointestinal sites. This suggested the potential of the immunotickets to serve as facile, effective and safe strategy to provide comprehensive immune responses against gastrointestinal infections and diseases.

Antigen

oil: Squalene

Cationic lipid: DDAB

PLGA

Figure 1 Miceocapsule (Immuniticket) and schematic illustration on immunoticket strategy References [1] Xia YF, Wu J, Su ZG, Ma GH, et al. Bridging the Systemic and Gastrointestinal Immune Responses via Oil-in-polymer Capsules, Adv. Mater., 30 (2018), 1801067.

4th CASNN Annual Meeting 2019

Haijun Yu

Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Haijun Yu is a P.I. and professor of pharmaceutics and in Shanghai Institute of Materia Medica, Chinese Academy of Sciences. He earned his Ph.D. from Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. After postdoc training at Ludwig-Maximillians University (Germany), UTSouthwestern Medical Centre at Dallas (USA) and Tohoku University (Japan), he was appointed as a staff member at Shanghai Institute of Materia Medica, Chinese Academy of Sciences since 2012, thereafter was promoted to a professor of pharmaceutics in 2016. He is engaged in non-viral gene delivery, stimuli-responsive drug delivery systems and cancer immunotherapy. He has authorized 90 publications including Nat Commun, Sci Immunol, Adv Mater and so on.

4th CASNN Annual Meeting 2019

93 Stimuli-activatable prodrug nanoparticles for cancer immunotherapy Bing Feng, Dangge Wang, Yaping Li, Haijun Yu*

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China Email: [email protected]

Introduction Immunotherapy has emerged as a promising modality for clinical cancer therapy due to its ability to initiate an antitumor immune response. However, the current immunotherapy is severely impaired by immunosuppression of host T-cell antitumor activity through the programmed cell death 1 ligand (PD- L1) and programmed cell death receptor 1 (PD-1) (PD-L1/PD-1) immune checkpoint or IDO-1. To this end, we had developed a tumor acidity and reduction microenvironment-activatable binary cooperative prodrug nanoparticle (termed as BCPN) for improved immunotherapy (Figure 1). Methods BCPN was prepared by self-assemble of a polyethylene glycol (PEG)-grafted OXA prodrug and a disulfide bond-crosslinked homodimer of NLG919. The PEGylated OXA prodrug and disulfide bond- crosslinked NLG919 dimer were both synthesised by following a procedure reported in our previous study. The immune modulation property of the prodrug nanoparticles was investigated by examining the immunogenic cell death induction (ICD), dendritic cell maturation and intratumoral infiltration of cytotoxic T lymphocytes (CTL), respectively. Results and Conclusion In this study, we demonstrated that activated OXA promoted intratumoral accumulation of cytotoxic T lymphocytes (CTLs) by triggering ICD of cancer cells. Meanwhile, NLG919 downregulates IDO-1- mediated immunosuppression and suppresses regulatory T cells. Most importantly, the prodrug nanoparticles shows much higher efficiency than free OXA or the combination of free OXA and NLG919 to regress tumor growth and prevent metastasis of mouse models of both breast and colorectal cancer. In comparison with the previously reported nanovectors, BCPN is of several unique advantages for cancer immunotherapy. First, BCPN displays high drug encapsulation efficacy and tuneable drug loading ratios by simply adjusting the feeding ratios of two prodrugs. Second, the PEGylated OXA prodrug is of superior sensitivity to the extracellular acidic pH of tumor. Upon reaching the tumor acidic microenvironment, BCPN switches to a positive surface charge following cleavage of the PEG corona, thereby improving tumor penetration and cellular uptake. The OXA prodrug and NLG919 dimer can be activated in the reduction microenvironment of tumor cells to avoid side effects. Reference 1. F Zhou, B Feng, H Yu, D Wang, T Wang, Y Ma, S Wang, Y Li, Tumor microenvironment- activatable prodrug vesicles for nano-enabled cancer immunotherapy combining immunogenic cell death induction and CD47 blockade. Adv Mater. 2018, 1805888. 2. D Wang, T Wang, H Yu, B Feng, L Zhou, F Zhou, B Hou, H Zhang, M Luo, Y Li. Engineered antibody nanoparticles overcome immunological tolerance to PD-L1 blockade therapy. Sci Immunol, 4 (2019), eaau6584. 3. B Feng, F Zhou, B Hou, D Wang, T Wang, Y Fu, Y Ma, H Yu, Y Li. Binary cooperative prodrug nanoparticles improve immunotherapy by synergistically modulating immune tumor microenvironment. Adv Mater. 2018, 1803001.

4th CASNN Annual Meeting 2019

Hao Cheng Drexel University

Dr. Hao Cheng (成昊) is an associate professor in the Department of Materials Science & Engineering at Drexel University. He received his B.E. and M.S. degrees in Chemical Engineering from Tsinghua University in 1999 and 2001, respetively.He completed his Ph.D. in Materials Science & Engineering from Northwestern University in 2005.Prior to joing Drexel University in 2012, he was a postdoctoral associate at Northwestern University and MIT. His laboratory focuses on cell membrane-derived hydrogels, long circulating nanoparticles, and biomaterials/biological materials for inducing antigen- specific immune tolerance. As a corresponding author, Dr. Cheng has published in journals such as ACS Nano, Nano Letters, Nature Communciations, and Advanced Drug Delivery Reviews. He is a receipient of the inaugural Nano Research Young Innovators Award in Nanobiotechnology in 2018.

4th CASNN Annual Meeting 2019

95 Nanomaterials for inducing antigen-specific immune tolerance Hao Cheng DREXEL UNIVERSITY,LeBow Engineering 344, 3141 Chestnut Street, Materials Science and Engineering

Available treatments for autoimmune diseases often require lifelong intervention and cause side effects. Induction of antigen-specific immune tolerance, which reduces autoreactive immune cells and/or generates antigen-specific regulatory T cells in patients, is a promising strategy for curing the diseases. Systemic administration of poly(lactic-co-glycolic acid) (PLGA) nanoparticles with autoantigen peptides have been demonstrated to induce antigen-specific immune tolerance in experimental autoimmune encephalitis (EAE), a murine model of multiple sclerosis. However, the same nanoparticles failed to alleviate the disease after local injection. Although therapeutics access immune cells efficiently via systemic administration, local administration has the potential advantage in spatiotemporally modulating immune cells in a well-controlled microenvironment. It is unknown whether any biomaterials carrying autoantigens without tolerogenic drugs can induce tolerance via local administration and what material properties are necessary. Addressing these questions will advance the design of nanomaterials for immune tolerance. We have found PLGA nanoparticles induced strong inflammatory responses after subcutaneous (s.c.) injection in mice, explaining their lack of efficacy using this injection route. After reducing the complement activation of nanoparticles, we show nanoparticles encapsulating MOG peptide can induce antigen-specific immune tolerance in EAE after disease onset via s.c. administration of the nanomaterials as well as i.v. injection. Immune cells in secondary lymphoid organs and the central nervous system were analysed to elucidate the mechanism of tolerance induction.

Key Words: Immunotherapy, immunoengineering, antigen-specific immune tolerance

4th CASNN Annual Meeting 2019

Haobo Pan

Shenzhen Institutes of Advanced Technology, CAS

PROF. HAOBO PAN completed his PhD studies at the University of Hong Kong in 2007, and carried out his postdoctoral research at the Li Ka Shing Faculty of Medicine in the University of Hong Kong from 2008 to 2010. In 2010, he promoted to Research Assistant Professor at the Department of Orthopaedics and Traumatology in the University of Hong Kong. In 2012, he was appointed as the Director of the Research Center in Human Tissues and organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science. Later, he was promoted as the Vice Director of the Institute of Biotechnology and Biomedicine and appointed as the Director of Shenzhen Key laboratory in Marine Biomaterials and the Director of Technology Center of Guangdong Province Marine Biological Materials Engineering. Now, he is appointed as Vice Director of the National Unit of Orthopaedic Biomaterials in China. His current research activities are focused on material chemistry, biomaterial synthesis and modification, marine biotechnology, biomaterial zoology and clinical assessment. He has published more than 100 papers in qualified international journals and served as board member of Bioactive Materials, ISRN Biomaterials and Journal of Osteoporosis and Physical Activity.

4th CASNN Annual Meeting 2019

97 Microenvironment pH of the Biodegradable Implants Can Modulate the Osteogenesis Both in vitro and in vivo Haobo Pan

4th CASNN Annual Meeting 2019

Hsing-Wen Sung National Tsing Hua University Department of Chemical Engineering

Hsing-Wen Sung is a Tsing Hua Distinguished Chair Professor, Department of Chemical Engineering, National Tsing Hua University. He received his PhD degree from the Department of Chemical Engineering/Biomedical Engineering Program, Georgia Institute of Technology in May 1988. His research interests are biomaterials, tissue engineering, and drug/gene delivery. Professor Sung has received numerous awards such as Fellow of American Institute for Medical and Biological Engineering, Fellow of International Union of Societies for Biomaterials Science and Engineering, Academician of Asia Pacific Academy of Materials, Ho Chin Tui Outstanding Research Award, National Science Council Outstanding Research Award, Professor Tsai-The Lai Award, Elsevier 2015 Biomaterials Best Paper Award, and 2016 TERMIS-AP Outstanding Scientist Award. He has been on the Editorial Boards of Journal of Controlled Release, Tissue Engineering, and Advanced Healthcare Materials; also, he has been serving as a Handling Editor for Biomaterials. Professor Sung has published 260 scientific papers and received 120 international patents. His published papers have over 14,500 citations with an H-index of approximately 70, according to Google Scholar.

Representative Publications: 1. Lin, Y. -J., Chen, C.-C., Chi, N.-W., Nguyen, T., Lu, H.-Y., Nguyen, D., Lai, P.-L.*, Sung, H.-W.*, "In situ self-assembling micellar depots that can actively trap and passively release NO with long- lasting activity to reverse osteoporosis," Advanced Materials. vol. 30, 1705605, 2018. 2. Wan, W.-L., Lin, Y.-J., Shih, P.-C., Bow, Y.-R., Cui, Q., Chang, Y., Chia, W.-T.*, Sung, H.-W.*, "An In Situ Depot for Continuous Evolution of Gaseous H2 Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis," Angew Chem Int Ed Engl. vol. 57, pp. 9875-9879, 2018. 3. Chuang, E.-Y., Lin, K.-J., Huang, T.-Y., Chen, H.-L., Miao, Y.-B., Lin, P.-Y., Chen, C.-T., Juang, J.-H*, Sung, H.-W.*, "An Intestinal "Transformers"-Like Nanocarrier System for Enhancing the Oral Bioavailability of Poorly Water-Soluble Drugs," ACS Nano. vol. 12, pp. 6389-6397, 2018. 4. Lin, P.-Y., Chiu, Y.-L., Huang, J.-H., Chuang, E.-Y., Mi, F.-L., Lin, K.-J., Juang, J.-H., Sung, H.- W.*, Leong, K. W.*, "Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy, "Advanced Science. vol. 5, 1701079, 2018. 5. Wan, W.-L., Lin, Y.-J., Chen, H.-L., Huang, C.-C., Shih, P.-C., Bow, Y.-R., Chia, W.-T.*, Sung,

H.-W.* "In Situ Nanoreactor for Photosynthesizing H2 Gas to Mitigate Oxidative Stress in Tissue Inflammation," Journal of the American Chemical Society, vol. 139, pp. 12923-12926, 2017.

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99 In situ gaseous H2 evolving systems for therapeutic applications Yu-Jung Lin1, Wei-Lin Wan1, Qinghua Cui1, Thanh-Ha Le1, I-Ting Sung2, Hsing- Wen Sung1*

1Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 2Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan Email: [email protected]

Hydrogen (H2) gas is able to reduce cytotoxic reactive oxygen species (ROS) that are generated in disease tissues. Inspired by natural photosynthesis, a nanoreactor (NR) that is composed of chlorophyll a (Chla), L-ascorbic acid, and gold nanoparticles (AuNPs) that are encapsulated in a liposomal (Lip) system that can evolve H2 gas in situ following photon absorption is used to alleviate inflammatory responses. Experimental results demonstrate that the Lip NR system that can [1] photosynthesize gaseous H2 has great potential for alleviating oxidative stress in tissue inflammation .

We also design a photo-driven H2-evolving liposomal nanoplatform (Lip NP) that comprises an upconversion nanoparticle (UCNP) that is conjugated with AuNPs via an ROS-responsive linker, which is encapsulated inside the liposomal system in which the lipid bilayer embeds Chla. The results obtained indicate the potential of using the Lip NP in the analysis of biological tissues, restoring their ROS homeostasis, possibly preventing the initiation and progression of diseases. Finally, a local delivery system that can provide a high therapeutic concentration of gaseous H2 continuously at inflamed tissues is proposed. The delivery system comprises PLGA microparticles that contain magnesium powder (Mg@PLGA MPs). The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of osteoarthritis [2] changes . Given the exciting advances that are mentioned above, we believe that these H2 bubble- evolving carrier systems may lead to significant technological breakthroughs in the treatment of various human pathologies.

References [1] W.L. Wan, Y.J. Lin, H.L. Chen, C.C. Huang, P.C. Shih, Y.R. Bow, W.T. Chia*, H.W. Sung*, In situ nanoreactor for photosynthesizing H2 gas to mitigate oxidative stress in tissue inflammation, J Am Chem Soc. 139 (2017), 12923–12926. [2] W.L Wan, Y.J. Lin, P.C. Shih, Y.R. Bow, Q. Cui, Y. Chang, W.T. Chia*, H.W. Sung*, An in situ depot for continuous evolution of gaseous H2 mediated by a magnesium passivation/activation cycle for treating osteoarthritis, Angew Chem Int Ed Engl. 30 (2018), 1705605.

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100

Hu Yang Virginia Commonwealth University

Dr. Hu Yang is Professor of Chemical and Life Science Engineering, Biomedical Engineering and Pharmaceutics, and the holder of Qimonda Endowed Chair of Engineering at Virginia Commonwealth University. He is a member of VCU Massey Cancer Center. Dr. Yang received his Bachelor of Engineering degree in Polymer from Sichuan University and his Ph.D. degree in Chemical Engineering from The University of Akron. He received postdoctoral training in Pharmaceutical Sciences at the University of Wisconsin-Madison. Dr. Yang received Wallace Coulter Young Investigator Award and NSF CAREER Award. Dr. Yang’s research is at the interface between engineering, materials science, medicine, and pharmaceutics. The interdisciplinary nature of his research allows him to blend pharmaceutics with engineering to generate new generation of therapeutics and formulations to improve therapeutic index & drug properties, achieve controlled release, enable non-invasive alternative administration and improve patient compliance. Dr. Yang has obtained multiple NIH R01 and R21 grants. His research has resulted in more than 80 peer-reviewed articles published in journals such as Nano Letters, ACS Nano, Biomaterials, Macromolecules, and Biomacromolecules. He is on the editorial board of Journal of Biological Engineering, Int. J. Polymeric Materials and Polymeric Biomaterials, and Smart Materials in Medicine.

4th CASNN Annual Meeting 2019

101 Peamotecan, a novel chronotherapeutic nanopolymer for brain cancer

Hu Yang (Invited Speaker)

Department of Chemical and Life Science Engineering, Virginia Commonwealth University, 737 North 5th Street, Richmond, Virginia 23219, United States Email: [email protected]

Introduction. Glioblastoma multiforme (GBM) is an ultimately lethal disease with a median survival of a little more than a year. Standard-of-care of GBM is surgery followed by chemoradiation. Progress in improving treatment has been slow with only incremental advances over the last several decades. New therapeutic approaches are therefore urgently needed. Herein, we have developed and tested a novel, “clickable” nanoconjugate formulation (PEAMOtecan) based on camptothecin (CPT) with chronotherapeutic and theranostic capabilities to establish proof-of- principle therapeutic effects in orthotopic mouse tumor models. While combining PEAMOtecan with other inhibitors and modalities, such as radiation, is our long-term goal, our more immediate one was to first test PEAMOtecan as monotherapy for efficacy in a mouse orthotopic glioma model. Methods. PEAMOtecan was first synthesized by click coupling CPT via disulfide and PEG linkers to PEAMO polymer that we reported previously [1]. Near-infrared (NIR) Cy5.5 labeled PEAMOtecan was also prepared via click chemistry for imaging. Release kinetics of CPT from PEAMOtecan was quantified with HPLC. Cell toxicity was tested on human glioma U1242/luc-GFP cells. Animal survival studies were also conducted. Mouse GL261/luc-DsRed glioma cells expressing luciferase and RFP reporters were injected into the brain of C57bl6 or NCr nu/nu mice as described [2]. Convection- enhanced delivery of PEAMO-APO-CPT (control) and PEAMOtecan was essentially done as described [2] with 10 l of conjugate delivered over 20 min (0.5 l /min) using positive pressure. Growth of intra-cranial tumors was monitored by bioluminescence imaging (BLI) using a Caliper- IVIS-200 instrument (PerkinElmer) and near-infrared (NIR) Cy5.5 live-animal imaging was done on a Pearl instrument (Li-Cor). Mouse imaging. Growth of intra-cranial tumors was monitored by bioluminescence imaging (BLI) using a Caliper-IVIS-200 instrument (PerkinElmer) and near-infrared (NIR) Cy5.5 live-animal imaging was done on a Pearl instrument (Li-Cor). Results and Conclusion. Camptothecin, a topoisomerase I inhibitor, targets and kills tumor cells by interfering with DNA replication resulting in DNA double-strand breaks (DSBs). Our studies show that PEAMOtecan is a highly modular polymer nanoformulation which protects covalently bound CPT until slowly being released over extended periods of time dependent on the chemical linker. In addition, a near-infrared (NIR) dye coupled to our polymer provided live-animal imaging capability and the ability to track tissue distribution and clearance of the injected polymers over time. PEAMOtecan administered by one-time, convection-enhanced delivery (CED) intra-tumorally using a catheter achieved superior distribution and extended drug release over time. We also show that PEAMOtecan significantly improves the survival of mice harboring intra-cranial tumors. Altogether, our modular nanoconjugate platform with time-released CPT combined with imaging allows for therapeutic evaluation in small animal tumor models.

References [1] O.Y. Zolotarskaya, et al, Synthesis and Characterization of Clickable Cytocompatible Poly(ethylene glycol)-Grafted Polyoxetane Brush Polymers, Macromolecules, 46 (2013) 63-71. [2] L. Biddlestone-Thorpe, et al., ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation, Clinical cancer research : an official journal of the American Association for Cancer Research, 19 (2013) 3189-3200.

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102

Huabing Chen

Soochow University

Huabing Chen is a Professor of Pharmaceutics, Soochow University. He received his PhD from Huazhong University of Science and Technology, China in 2008. From 2008 to 2012, he worked as a postdoctoral fellow at the University of Texas Southwestern Medical Center at Dallas and University of Tokyo. He was appointed as a full professor at College of Pharmaceutical Sciences, Soochow University in 2012. He has published over 50 peer-reviewed articles. His current research focuses on multifunctional nanocarriers for cancer-targeted drug delivery, cancer phototherapy, as well as early cancer imaging. He was awarded Excellent Young Scientists Fund by the National Natural Science Foundation of China in 2014, and was also selected as a Young Scholar by Chang Jiang Scholars Program of Ministry of Education in 2016.

4th CASNN Annual Meeting 2019

103 Bifunctional BODIPY nanoparticles for cancer phototherapy Huabing Chen

Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China. Email: [email protected]

Highly potent photosensitizers are of great interest for achieving selective cancer phototherapy. However, the photosensitizers still suffer from limited tumor suppression in phototherapy. A major challenge still remains in exploring an rational approach to maximize the photo-induced cell damage through optimized photoconversion behaviors of photosensitizers. We report a few rational designs of boron dipyrromethene (BODIPY)-based nanoparticles that can induce dually cooperative phototherapy upon light exposure. In the self-assembled nanoparticles, cisplatin as a heavy atom source was coordinated into BODIPY to boost both singlet oxygen and photothermal effect for generating both photodynamic therpay (PDT) and photothermal therapy (PTT). Meanwhile, we also found that the conjugated coupling of BODIPY monomers into dimeric BODIPY or trimeric BODIPY in the nanoparticles led to the primary photoconversion from fluorescence to singlet oxygen for PDT or photothermal effect for PTT, respectively. Moreover, the well-organized aggregation of BODIPY within the polymeric vesicles also induced the primary photoconversion into thermal effect together with slight siglet oxygen generation. These designs of BODIPY-based nanoparticles dramatically contributed to the tumor ablation through the cooperative anticancer efficiency, and can serve as valuable phototherapeutic paradigms for potent cancer phototherapy.

References [1] S. Ye, J. Rao, S. Qiu, J. Zhao, H. He, Z. Yan, T. Yang, Y. Deng, H. Ke, H. Yang, Y. Zhao, Z. Guo, H. Chen. Rational design of conjugated photosensitizers with controllable photoconversion for dually cooperative phototherapy, Adv. Mater. 30 (2018) 1801216. [2] H. He, S. Ji, Y. He, A. Zhu, Y. Zou, Y. Deng, H. Ke, H. Yang, Y. Zhao, Z. Guo, H. Chen. Photoconversion-tunable fluorophore vesicles for wavelength-dependent photo-induced cancer therapy, Adv. Mater. (29) 2017, 1606690. [3] Z. Guo, Y. Zou, H. He, J. Rao, S. Ji, X. Cui, H. Ke, Y. Deng, H. Yang, C. Chen, Y. Zhao, H. Chen. Bifunctional platinated nanoparticles for photo-induced tumor ablation, Adv Mater, 2016, 28, 10155-10164.

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104

Huaping Xu

Tsinghua University

Huaping Xu received his Bachelor degree in 2001 and Ph.D. degree in 2006 in Jilin University, China, under the supervision of Prof. Xi Zhang. In 2006, he joined Prof. David N. Reinhoudt and Prof. Jurriaan Huskens’s group at University of Twente, The Netherlands, as a postdoc. Since July 2008, he has worked at Department of Chemistry, Tsinghua University, China. He was promoted to full professor in 2014. In 2014, he received the Natural Science Fund for Outstanding Young Scholars from NSFC. In 2017, he was enrolled in Leading Talent of National High-level personnel of special support program (“people plan”). He has served for Associate Editor of ACS Biomaterials Science & Engineering since January 2017. His current research is focused on selenium/tellurium-containing polymers.

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105 Self-assembly and anticancer activity of selenium-containing compounds Tianyu Li, Huaping Xu

Department of Chemistry, Tsinghua University, Beijing, 100084, People’s Republic of China Email: [email protected]

Selenium-containing polymers have been applied in the construction of responsive nanomedicine carriers for anticancer drug delivery and controlled release. Moreover, selenium may possess anticancer activity on its own based on the ability of regulating redox balance in human body. Here, we have studied the anticancer activity and the mechanism of selenium-containing compounds, developed a series of selenium-containing self-assemblies with concise structures. The assemblies show good anticancer activity and low side effects, thus exhibiting great potential for clinical cancer treatment. Selenium-platinum coordination assemblies with concise structures were developed by coordination between selenium-containing molecules and platinum compounds. The assemblies exhibited good anticancer activity and low side effects with a mechanism of inducing high levels of reactive oxygen species (ROS) to kill cancer cells. The interactions between selenium and metals other than platinum were also explored. Selenium-containing compounds were found to simultaneously reduce and stabilize gold(III), and prepare uniform 2 nm gold nanoparticles in one single step. The selenium prepared gold nanoparticles induced cancer cell apoptosis by regulating intracellular ROS concentration, thus inhibiting tumor growth. In addition, selenium was found to coordinate with metals such as nickle, copper, and zinc, resulting in coordination complexes with anticancer activity. The cancer immunoactivity of organic seleninic acid was recently revealed, which suppressed the expression of human leukocyte antigen E (HLA-E) in cancer cells, and then activated the immunoactivity of nature killer (NK) cells. On the basis of this mechanism, diselenide-pemetrexed assemblies were developed to combine cancer immunotherapy with radiotherapy and chemotherapy. Radiation will generate oxidative radicals and oxidize diselenide group to selenic acid and release chemotherapy drug pemetrexed molecules. The combination therapy improved the antitumor efficacy of immunotherapy while maintaining the low side effects, which broadens the application of selenium- containing compounds in cancer immunotherapy. Self-assembly behavior and anticancer activity of selenium-containing compounds were explored. A series of selenium-containing assemblies with concise structures were developed, including selenium-platinum coordination complexes, selenium- prepared gold nanoparticles, and diselenide-pemetrexed assemblies. These systems exhibit good anticancer activity as well as low side effects, thus possessing great potential for clinical applications. The study enriches the knowledge of physiological activity of selenium, and opens new avenues for selenium-containing compounds in cancer treatment.

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106

Jianxun Ding

Changchun Institute of Applied Chemistry, Chinese Academy of Sciences

Dr. Jianxun Ding is an Associate Professor in the Changchun Institute of Applied Chemistry (CIAC), Chinese Academy of Sciences (CAS). He received his B.S. degree from the University of Science and Technology of China (USTC) in 2007 and obtained his Ph.D. degree in the CIAC, CAS, in 2013 under the supervision of Prof. Xuesi Chen. During 2017−2019, he worked with Prof. Omid C. Farokhzad and Prof. Jinjun Shi from the Brigham and Women's Hospital, Harvard Medical School as a Postdoctoral Research Fellow. He was awarded the 2012 President Excellence Award of CAS. His research focuses on (1) synthesis of functional biodegradable polymers, (2) development of smart polymer platforms for controlled drug delivery, (3) exploitation of polymer-based adjuvants for immunotherapy, and (4) preparation of polymer scaffolds for regenerative medicine.

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107 Polypeptide nanomaterials for cancer therapy Jianxun Ding*, Xiuli Zhuang, Xuesi Chen

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China Email: [email protected]

Polypeptides with excellent biocompatibility and biodegradability are composed of various amino acids, which have broad applications in different biomedical fields, such as controlled drug release and tissue engineering [1]. For controlled drug delivery, our team has innovatively designed and synthesized a series of functional polypeptide nanomaterials as nanoscale drug delivery systems in the past six years [2−8]. Drugs with different properties can be loaded into the polypeptide nanomaterials through the selection of core structures and high-selectively released in the cells triggered by the degradation of polypeptides under the stimulation of the intracellular microenvironments of cancer cells [2,9]. On this basis, by regulating the surface properties of polypeptide nanomaterials (charge or targeting ligands), the nanocarriers are further endowed with the characteristics of high adhesion and permeability, targeting, charge reversal, and/or variable particle size, so as to enhance the accumulation and permeation of nanomedicines in the tumor tissue and high-selectively release drugs in the cancer cells [3−5]. The studies provide a new and efficient platform for precision cancer therapy. In the follow-up study, we will combine immunotherapy and other advanced treatment modalities with functional polypeptide nanomedicines to further improve the therapeutic effects toward cancers, and lay a theoretical and experimental foundation for their clinical transformation.

References [1] J. Ding, C. Xiao, Z. Tang, X. Zhuang, X. Chen, Highly efficient "grafting from" an α-helical polypeptide backbone by atom transfer radical polymerization, Macromol. Biosci. 11 (2011) 192−198. [2] J. Ding, F. Shi, C. Xiao, L. Lin, L. Chen, C. He, X. Zhuang, X. Chen, One-step preparation of reduction-responsive poly(ethylene glycol)-poly (amino acid)s nanogels as efficient intracellular drug delivery platforms, Polym. Chem. 2 (2011) 2857−2864. [3] J. Chen, J. Ding, Y. Wang, J. Cheng, S. Ji, X. Zhuang, X. Chen, Sequentially responsive shell- stacked nanoparticles for deep penetration into solid tumors, Adv. Mater. 29 (2017) 1701170. [4] J. Chen, J. Ding, W. Xu, T. Sun, H. Xiao, X. Zhuang, X. Chen, Receptor and microenvironment dual-recognizable nanogel for targeted chemotherapy of highly metastatic malignancy, Nano Lett. 17 (2017) 4526−4533. [5] H. Guo, F. Li, W. Xu, J. Chen, Y. Hou, C. Wang, J. Ding, X. Chen, Mucoadhesive cationic polypeptide nanogel with enhanced penetration for efficient intravesical chemotherapy of bladder cancer, Adv. Sci. 5 (2018) 1800004. [6] H. Guo, W. Xu, J. Chen, L. Yan, J. Ding, Y. Hou, X. Chen, Positively charged polypeptide nanogel enhances mucoadhesion and penetrability of 10-hydroxycamptothecin in orthotopic bladder carcinoma, J. Control. Release 259 (2017) 136−148. [7] J. Ding, J. Zhang, J. Li, D. Li, C. Xiao, H. Xiao, H. Yang, X. Zhuang, X. Chen, Electrospun polymer biomaterials, Prog. Polym. Sci. 90 (2019) 1−34. [8] S. Li, T. Zhang, W. Xu, J. Ding, F. Yin, J. Xu, W. Sun, H. Wang, M. Sun, Z. Cai, Sarcoma- targeting peptide-decorated polypeptide nanogel intracellularly delivers shikonin for upregulated osteosarcoma necroptosis and diminished pulmonary metastasis, Theranostics 8 (2018) 1361−1375. [9] F. Shi, J. Ding, C. Xiao, X. Zhuang, C. He, L. Chen, X. Chen, Intracellular microenvironment responsive PEGylated polypeptide nanogels with ionizable cores for efficient doxorubicin loading and triggered release, J. Mater. Chem. 22 (2012) 14168−14179.

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108

Jie Zheng The University of Texas at Dallas

Dr. Jie Zheng currently holds Cecil H. and Ida Green Professor in Systems Biology in the chemistry department of The University of Texas at Dallas and also an adjunct full professor in the urology department at UTSW medical center. His research interest is focused on fundamental understandings of physiology at the nano scale and develop renal clearable nanomedicines to address challenges in the early disease detection and treatment. Since joining UT Dallas in 2008, he has more than 50 publications in peer-reviewed journals including Nature Nanotech, Nature Reviews Materials. He is also the founder of ClearNano Inc. for commercializing the next generation of renal nanomedicines.

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109 Renal clearable nanomedicines: from fundamentals to applications Jie Zheng

Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, USA, *e-mail: [email protected]

Through investigation of nanoparticle transport and interactions in vivo not only allow us to advance our fundamental understandings of physiology at the nanoscale but also help broaden their biomedical applications and accelerate their clinical translation. In this talk, I will present how to use renal clearable nanomedicines to advance understandings of nephrology at the sub-nm regime as well as how to apply these understandings to deliver anticancer drugs or probe an overlooked liver function in the modulation of nanoparticle transport and disease targeting.

References: [1] X.Y. Jiang, B. J. Du., J. Zheng, Glutathione-mediated biotransformation in the liver modulates nanoparticle transport, Nature Nanotechnology, 2019, https://doi.org/10.1038/s41565-019-0499- 6 [2] B.J. Du, M.X. J. Zheng, Transport and interactions of nanoparticles in the kidneys, Nature Reviews Materials, 2018, 358 [3] C.Q. Peng, J. Xu, M.X. Yu, X.H. Ning, Y.Y. Huang, B.J. Du, E. Hernandez, P. Kapur, J-T Hsieh and Jie Zheng Tuning in vivo transport of anticancer drugs with renal-clearable gold nanoparticles, Angew. Chem. Int. Ed. 2019. 10.1002/anie.201903256 [4] M.X. Yu, J. Xu, J. Zheng, Renal Clearable Luminescent Gold Nanoparticles: From Bench to Clinics, Angew. Chem. Int. Ed., 2019, 4112-4128 [5] B.J. Du, X.Y Jiang, A. Das, Q.H Zhou, M.Y Yu, R.C Jin, J. Zheng ,Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime, Nature Nanotechnology, 2017, 1096

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110

Kanyi Pu Nanyang Technological University

Dr. Kanyi Pu has been an Associate Professor in the School of Chemical and Biomedical Engineering (SCBE) at Nanyang Technological University since June 2015. He did his MS (2007) at Fudan University in China, and his PhD (2011) at National University of Singapore in Singapore. He moved to Stanford University School of Medicine for his postdoctoral study in 2011. Dr. Pu has published more than 145 journal papers, 3 book chapters and 6 patents. With a h-index of 61 (August 2019). He has won a number of awards for his creative work, including the distinguished lectureship award from the Chemistry Society of Japan, Wiley award for contribution in bioscience, young investigator travel award, and young innovator award in nanobiotechnology by Nano Research. Dr. Pu serves as the associate editor for ACS Applied Polymer Materials and Biomaterials Research, and as the Young Star Editor for Nano Research. He also sits on the Editorial Advisory Board of many high-impact multidisciplinary journals including Advanced Functional Materials, Bioconjugate Chemistry, ACS Applied Bio Materials, Advanced Biosystems, and ChemNanoMat.

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111 Molecular optical reporters for ultrasensitive afterglow imaging and early diagnosis Kanyi Pu

Optical imaging plays a crucial role in biology and medicine. However, the need for real-time light excitation during imaging produces tissue autofluorescence, which compromises imaging sensitivity and specificity in living subjects. Meanwhile, optical agents are often retened in living bodies, posing additional toxicity issue. In this seminar, I will introduce molecular afterglow reporters with long- lasting luminescence after removal of light excitation for ultrasensitive in vivo imaging, followed by discussion on how to design renal-clearable optical reporters for early diagnosis of kidney diseases. Molecular afterglow reporters are developed based on purely organic semiconducting polymer nanoparticles (SPNs) that can store photon energy via chemical defects and gradually emit near- infrared (NIR) afterglow luminescence at 780 nm after light pre-irradiation. The in vivo afterglow of SPNs has the signal to background ratio (SBR) more than two orders of magnitude higher than NIR fluorescence, enabling rapid detection of tiny peritoneal metastatic tumors. The structural diversity of SPNs allows them to monitor temperature during photothermal cancer therapy and detect biomarkers of interest in living mice. To detect acute kidney injury (AKI), molecular renal probes (MRPs) with high renal clearance efficiency are developed. MRPs specifically activate their NIR/chemiluminescence signals towards the prodromal biomarkers of AKI, enabling the first example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI. These studies thus provide the basis for an entirely new class of molecular optical reporters with ultrahigh sensitivity and high translational potential for early diagnosis.

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112

Ke Cheng UNC/NCSU State University

Dr. Ke Cheng is Professor in the UNC/NCSU joint Department of Biomedical Engineering and Professor in the Department of Molecular Biomedical Sciences NC State University. He is an adjunct professor at the UNC Eshelman School of Pharmacy. Ke also serves as the co- director of the functional tissue engineering program at the Comparative Medicine Institute. Dr. Cheng’s formal education began with a B.S. in Pharmaceutical Engineering from the Zhejiang University and Chu Kochen Honors College, followed by a Ph.D. degree in Biological Engineering from University of Georgia and post-graduate training/junior faculty experiences at UCLA School of Medicine and Cedars-Sinai Medical Center. Dr. Cheng's research results have been summarized into publications in journals like Lancet, Nature BME, Nature Comms, Science Advances, J of Clinical Investigation, Circulation, Circulation Research, Eur Heart J, J Am Coll Cardiology, ACS Nano, Adv Func Mater, Biomaterials etc. His work has been directly translated into two awarded investigational new drug applications (IND) and licensed to three biotech companies. Dr. Cheng is Fellow of American Heart Association and Fellow of AIMBE. Dr. Cheng is Associate Editor of the Journal of Cellular and Molecular Medicine (Wiley) and an Editorial Board Member of Circulation Research.

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113 Application of nanotechnologies for enhanced stem cell therapies

Shiqi Hu1, 2, Zhenhua Li1, 2, Ke Huang1, Teng Su1,2, Junnan Tang1,2, Li Qiao1,2, Ke Cheng1, 2 1 Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, 27607, United States. 2 Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, and North Carolina State University, Raleigh, NC, 27606, United States. Email: [email protected]

Cardiovascular disease outranks all causes of death in the United States, including cancer. People are racing to develop new approaches for cardiac regeneration. Stem cell transplantation showed an enhanced good safety profile to date, but still lack of reproducible results in clinical trials. Recently, stem cell secretome, including exosomes, growth factors and cytokines, has shown efficacy in reducing heart infarcted area. Here, we will discuss the development of nanotechnology-based stem cell therapy in cardiac diseases.Direct transplantation of stem cells improves the cardiac function, however, few of the transplanted cells engraft and survive, and even fewer directly differentiate. Several types of stem cells have been proven that the paracrine effect contribute to their therapeutic effect. A broad spectrum of growth factors, cytokines and Figure 1. Stem cell therapy and nanotechnology-based exosomes are gradually gaining stem cell therapy. attention and have been demonstrated to exert beneficial effects in cardiac disease. To bypass the safety issue and low engraftment of stem cell delivery, a series of secretome loaded nanoparticles and modified exosomes have been designed and applied on myocardial infarction in our lab. As shown in Figure 1, cell membranes are usually used to cloak nanoparticles to achieve long circulation. Other strategies are designed for targeted delivery: 1) Magnetic systems are generally applied to achieve magnetic field- induced high drug concentration in area of interest by loading secretome in magnetic particles. 2) Platelet mimics are prepared due to activated platelets can infiltrate specifically into the ischaemic/reperfused myocardium. 3) Cardiac homing peptides or antibodies are anchored onto nanoparticles or exosomes to generate homing nanoparticles or exosomes for intravenous injection. Stem cell therapy for cardiac disease is promising, but controversial due to poor reproducible therapeutic effect and safety concerns. Nanotechnology-based stem cell therapy is highly translational not only because it can bypass unresolved matters of cell therapy, but also the design and manipulation of the secretome can greatly decrease the effective dose and increase the efficacy. By applying these approaches to the infarcted heart, there was a significant improvement in outcomes with reduced scar size and enhanced cardiac function.

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114

Ke Zhang Northeastern University

Dr. Ke Zhang obtained his BS degree in 2005 in Applied Chemistry from Nanjing University of Technology, China. He then studied polymer chemistry with Prof. Karen Wooley at Washington University in St. Louis focusing on shell-crosslinked knedel-like nanoparticles and gene delivery, and obtained a PhD in Chemistry in 2009. Thereafter, Dr. Zhang was a postdoctoral fellow in the laboratory of Prof. Chad Mirkin at Northwestern University to develop hollow spherical nucleic acids, a carrier-free platform for gene regulation. In 2012, Dr. Zhang joined Northeastern University and became an Associate Professor of Chemistry in 2017. His current research includes the design and synthesis of unique polymer superstructures, nucleic acid-polymer conjugates, and nanomedicine. Dr. Zhang received the 2018 ACS PMSE Young Investigator Award, the 2018 Nano Research Young Investigator Award, an ACS PRF Doctoral New Investigator Award, and an NSF CAREER award.

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115 Engineering Endothelial Leakiness With Nanoparticles Ke Zhang

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116

Kui Luo Sichuan University

Kui Luo, Ph.D, Professor in West China Hospital and National Engineering Research Center for Biomaterials, Sichuan University, China. Dr. Luo obtained his PhD from the National Engineering Research Center for Biomaterials, Sichuan University in 2009 under the supervision of Prof. Zhongwei Gu, and then as an assistant professor in this center. From 2009 to 2011, he carried out his postdoctoral work on polymeric nanomedicines at the Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, USA under the supervision of Prof. Jindrich Kopecek (Distinguished professor). Dr. Luo was promoted to an associate professor in 2012 and Full Professor in 2013 in Sichuan University. From 2016, he is also a Full Professor and PI in Huaxi MR Research Center (HMRRC), Functional and molecular imaging Key Laboratory of Sichuan Province, Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China. Dr. Luo has authored over 80 peer- reviewed SCI papers, 10 patents, 4 chapters and 10 fundings. Dr. Luo’s research in the past few years has been focused on stimuli and biodegradable polymeric gene/drug delivery vehicles and imaging probes for cancer diagnose and therapy. The main thrust of his research is the study of the stimuli- responsive, biodegradable and functionalized synthetic macromolecules (including linear and dendritic polymers) as potential cancer therapeutic and diagnostic agents, and the relationships between their actions and structural features. Those interdisciplinary approaches involve polymer chemistry, organic and physical chemistry, pharmaceutics, imaging, biomedicine and molecular biology.

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117 Tumor microenvironment-responsive dendritic polymers based nanoplatforms for drug delivery Dayi Pan, Kui Luo* Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital, and National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610041, China *E-mail: [email protected]

Tumor microenvironment (TME)-responsive drug delivery systems that deliver a drug in spatial-, temporal- and dosage-controlled patterns have become a promising way to realize tumor-specific treatment[1, 2]. We moved on to design a series of biodegradable dendritic polymers for multiple stimuli-responsive drug delivery. These nano-platforms are shown that exhibit good biocompatibility and significant antitumor efficacy. Furthermore, these nano-platforms conjugated doxorubicin, gemcitabine, paclitaxel and oxaliplatin through pH-sensitive hydrazone bond, N, O-coordination and enzyme-sensitive GFLG linker to prepare a series of TME-responsive nanoscale drug delivery systems. Systemic delivery of dendronized PEG-platinum (II) resulted in 25-fold higher accumulated platinum into tumor than clinic agent at 36 h post-injection due to the enhanced permeability and retention (EPR) effect, which far higher than the reported TME-responsive drug delivery systems. Then we designed prepared a series of TME-responsive and reversible addition-fragmentation chain transfer (RAFT) polymerized branched HPMA nano-platforms with Gd(III) chelating, drug conjugation and cRGDyK functionalization for magnetic resonance imaging and targeted therapy. Finally, we explored systematically the relationship between the structure and their behaviors for drug delivery, and found that amphiphilic dendronized polymers with a moderate HLB value display enhanced stability and highly efficient tumor retention. These high-performance TME-responsive dendritic polymers based nano-platforms may be employed as a safe and efficient multiple stimuli-responsive drug delivery systems for diagnosis and therapy of cancer.

References [1] T. Ramasamy, H.B. Ruttala, B. Gupta, B.K. Poudel, H.-G. Choi, C.S. Yong, J.O. Kim, Smart chemistry-based nanosized drug delivery systems for systemic applications: A comprehensive review, Journal of Controlled Release, 258 (2017) 226-253. [2] J. Shi, P.W. Kantoff, R. Wooster, O.C. Farokhzad, Cancer nanomedicine: progress, challenges and opportunities, Nature Reviews Cancer, 17 (2016) 20.

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118

Lee Jia

Fuzhou University

Dr. Lee Jia is currently Distinguished Professor and “The China Recruitment Program of Global Experts”, and the founding Director of Cancer Metastasis Alert & Prevention Center at Fuzhou University, China. Prior to this position, he was the Senior Project Officer/ Senior Pharmacologist at NIH/USA. Dr. Jia is the Fellow of the American Association of Pharmaceutical Scientists (AAPS). Within AAPS, he was vice-Chair and Chair of the Section of Drug Design & Discovery of AAPS (2009-2012).

Dr. Jia obtained his PhD in Pharmacology in 1994 under supervision of Dr. Robert Furchgott (the 1998 Nobel Laureate) of the State University of New York, USA. His research interests cover many areas of pharmaceutical sciences, and he pioneers the new area of cancer metastasis chemoprevention for safe and effective prevention of cancer metastasis. He has contributed >200 peer-reviewed papers to high-impact journals including Science, Nature and PNAS. He is recognized as one of the 2014- 2018 highly-cited Chinese scholars by Scopus. Dr. Jia serves for Editorial Boards of peer-reviewed journals.

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119 The challenge problems of pharmaceutical bionanotechnology Yusheng Lu, Chen Zhang, Chunlian Zhong, Min Lin, Lee Jia (贾力) Marine Drug R&D Center, Institute of Oceangraphy, MinJiang University/ Cancer Metastasis Alert and Prevention Center, and Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350116, China. Email: [email protected]; [email protected]

Bionanotechnology has been developed for prolonging circulating half-time of drugs and target delivery of cytotoxic anti-cancer drugs long before the USA National Nanotechnology Initiative (NNI) announced in January 2000, and the launch of the NCI Alliance for Nanotechnology in Cancer in September, 2003. Today, because our understandings of pathology and theranostics of various diseases have been advanced based on Bionanotechnology, many biomedical achievements are obtained. However, to precisely and accurately reach its theranostics targets, the bionanotechnology-derived pharmaceuticals still face many challenges to overcome: 1) they must be biostable in the blood; 2) they must be able to recognize and bind/interact with their specific targets to avoid any off-target side effects; 3) they must be able to escape from immune attach; 4) they must flee from liver accumulation and hepatobiliary elimination, where majority of administered nanoparticles are sequestered by Kupffer cells when blood velocity decreases more than 100 folds. This presentation summarizes the current understandings of target problems that bionanotechnology faces, and proposes strategies to overcome these problems.

References: 1. Jia, L. Global governmental investment in nanotechnologies. Curr. NanoScience 1: 263-6, 2005. 2. Gao, Y. Xie, J., Chen, H., Gu, S., Zhao, R., Shao, J., Jia, L. Nanotechnology-based intelligent drug design for cancer metastasis treatment. Biotech Adv. 32:761-777, 2014. 3. Gao, Y., Shao, J., Jiang, Z., Chen, J., Gu, S., Yu, S., Zheng, K., Jia, L. Drug enterohepatic circulation and disposition: constituents of systems pharmacokinetics. Drug Disc. Today 19:326-340, 2014. 4. Tsoi et al., Mechanism of hard-nanomaterial clearance by the liver. Nat. Materials 15:1212-21, 2016.

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120

Liangfang Zhang

UC San Diego

Dr. Liangfang Zhang received his B.E. and M.S. degrees in Chemical Engineering from Tsinghua University, and his Ph.D. in Chemical & Biomolecular Engineering from the University of Illinois at Urbana-Champaign in 2006 under the supervision of Prof. Steve Granick. He was a postdoctoral associate in the laboratory of Prof. Robert Langer at MIT during 2006-2008. He joined the Department of Nanoengineering at UC San Diego as an Assistant Professor in July 2008 and was promoted to Professor in July 2014. Dr. Zhang’s research interests focus on biomimetic nanomedicine, with a particular interest in creating and evaluating nanostructured biomaterials for drug delivery, detoxification and vaccination for treatment of infectious diseases and cancer. He has published 197peer-reviewed articles and holds 96 issued/pending patents. He received the ACS Victor K. LaMer Award (2009), UCSD Jacobs School of Engineering Best Teacher Award (2011), ACS Unilever Award (2012), MIT Technology Review’s TR35 Innovator Award (2013), AIChE Allan P. Colburn Award (2014), AIMBE Fellow (2015), Popular Science’s Brilliant 10 Award (2016), U.S. Department of State ASPIRE Award (2017), Kabiller Young Investigator Award (2017), and AAAS Fellow (2018).

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121 Nanomachines biointerfacing via cell membrane cloaking for active delivery and removal

Liangfang Zhang

Department of Nanoengineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Email: [email protected]

The emerging nanotechnology in biomedicine has sparked new hope for the treatment and diagnosis of various important human diseases. However, development of functional nanomaterials and nanomachines can be encumbered by unanticipated material properties and biological events, which can negatively impact their effectiveness when introduced into complex, physiologically relevant systems. Herein, the preparation of nanodevices (e.g. nanoparticles, nanomotors, etc) enclosed in the plasma membrane of natural human cells is reported. The resulting cell membrane-coated nanodevices are demonstrated to possess many surface functions of natural cells via studies of interactions with plasma proteins, cells, tissues, and microorganisms. Such multifaceted cell- mimicking properties can be attributed to the preservation of biomembrane on nanodevice surfaces, which facilitates the display of intricate biochemistry that is difficult to replicate using conventional functionalization approaches. As the platform is entirely biocompatible and biodegradable, it can be applied toward a myriad of biomedical applications, including active drug delivery and detoxification, where the vast implications of cell surface properties may benefit a variety of disease treatments. This talk will highlight the integration of the cell membrane coating technology with the self-propelled nanomotor technology to create a biomimetic nanomachine that can actively deliver drugs/antigens to target cells and tissues, while removing cell-specific toxins and pathogens from the environment.

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Ling Peng Aix-Marseille University

Dr. Ling Peng is a CNRS research director in the Interdisciplinary Center on Nanoscience in Marseille at Aix-Marseille University in France. She carried her undergraduate study at Nanjing University in China, her PhD at Swiss Federal Institute of Technology in Zurich, Switzerland, and her postdoctoral research at University of Strasbourg in France. She was recruited as a research scientist in CNRS in 1997, promoted as a CNRS research director in 2008, and then 1st class Research Director in 2015. Dr. Ling PENG has been working actively at the interface of chemistry and biology, and in particular, developing functional dendrimers for biomedical applications, molecular probes for exploring biological events and drug discovery. She was awarded with the Prize of Dr & Mme Henri Labbé of the French Academy of Sciences, and her research group has been awarded and labelled by “La Ligue Contre le Cancer” in France.

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123 Self-assembling supramolecular dendrimers for biomedical applications Ling Peng

Centre Interdisciplinaire de nanoscience de Marseille Aix-Marseille University, CNRS, Marseille, France

Self-assembly is a fundamental concept and a powerful approach for creating new functional materials, and the application of self-assembly to engineer nanomaterials for drug delivery is widely expected to bring novel perspectives in nanomedicine. We will report our recent efforts to establish innovative self-assembling dendrimer nanosystems as drug carriers, gene vectors and bioimaging probes for biomedical applications.1-3 Starting with small amphiphilic dendrimers, we have constructed modular, responsive and adaptive dendrimer nanosystems which are able to carry either hydrophobic anticancer drugs 1 or hydrophilic nucleic acid therapeutics 2 for treating cancer and overcoming drug resistance. Also, the dendrimer nanosystems are able to deliver imaging agents for higher imaging quality by harnessing the multivalent feature of dendrimer and the EPR effect of the tumor microenvironment.3 The concept of self-assembling supramolecular dendrimers has hence opened new avenues in nanotechnology based biomedical applications for treating various diseases.

References [1] Wei et al, Proc. Natl. Acad. Sci. U.S.A. 2015, 112, 2978; Zhou et al, Chem. Comm. 2018, 54, 5956– 5959. [2] Liu et al, Angew. Chem. Int. Ed., 2014, 53, 11822; Chen et al, Small 2016, 12, 3667; Liu et al, Adv. Funct. Mater. 2016, 26, 8594–8603; Dong et al, J. Am. Chem. Soc. 2018, 140,16264. [3] Garrigue et al, Proc. Natl. Acad. Sci. U.S.A. 2018, 115,11454.

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Prof. Lintao Cai

Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT)

Lintao Cai, Professor, received his Ph.D. degree in Physical Chemistry from Xiamen University in 1995, then worked at Nanjing University and in State Key Laboratory of Bioelectronics at Southeast University. From 1999 to 2001, he was sponsored by Japan Society of the Promotion of Science (JSPS) and worked as Research Fellow in Institute of Scientific and Industrial Research at Osaka University. He Joined the Center for Nanoscale Science and Technology at Rice University in 2001 and Department of Electrical Engineering at the Pennsylvania State University between 2002 and 2007, and then worked as Research Scientist at Emitech, Inc. Dr. Cai’s scientific research areas include nanomedicine, functional materials, chemical biology and biomedical engineering. He explores theranostic nanoparticles, drug delivery system and self-assembly technique using various building blocks for the development of smart materials, molecular diagnosis, in vivo cancer imaging and targeted therapy, personalized medicine and other applications.

He has more than 124 publications with 4000 citations in peer reviewed Journals, including JACS, Nano Lett., ACS Nano, Adv Mater, Chem. Mater, Biomaterials, J Control Release，Theranostics, etc. He obtains 4 PCT international patents and 54 authorized patents. He is a member of Chinese Chemical Society (CCS), Royal Society of Chemistry (RSC), the American Chemical Society (ACS) and Materials Research Society (MRS)

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125 Cell membrane mimicking nanoparticles with cancer targeting and immune recognition Lintao Cai*

Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab for Biomaterials Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology (SIAT) Chinese Academy of Sciences, Shenzhen 518055, P. R. China E-mail: [email protected]

The precision nanomedicine significantly relies on the development of multifunctional agents to integrate cancer targeting, imaging, therapeutics and immune regulation. We report here a series of cell membrane mimicking nanoparticles for cancer targeting and immune recognition. 1) a cancer cell membrane−cloaked nanoparticle system as a theranostic nanoplatform. Benefited from the functionalization of the binding adhesion molecules from cancer cell membranes, the nanosystem demonstrated specific homologous targeting to cancer cells for cancer-targeted imaging and phototherapy. 2) a cell-membrane immunotherapy strategy could eliminate primary tumors and inhibited distant tumors by using natural killer (NK) cell membrane cloaked nanoparticles (NK-NPs). The NK cell membranes enabled the NK-NPs to target tumors and could induce immunogenic cell death (ICD) to activate DC/T cells and enhanced pro-inflammatory M1-macrophages polarization to produce antitumor immunity. 3) the plasma membrane of macrophage camouflaged nanoparticles, MDINPs, could penetrate BBB and selectively accumulate at tumor site, and kill tumor cells by photothermal effect. 4) the T cell membrane mimicking nanoparticles based bioorthogonal chemistry provide an alternative artificial targeting strategy for tumor targeting photothermal therapy.

References [1] Z. Chen, P.F. Zhao, Z.Y. Luo, M.B. Zheng, H. Tian, P. Gong, G.H. Gao, H. Pan, L.L. Liu, A.Q. Ma, H.D. Cui, Y.F. Ma, L.T. Cai. Cancer Cell Membrane-Biomimetic Nanoparticles for Homologous- Targeting Dual-Modal Imaging and Photothermal Therapy. ACS Nano, 10 (2016) 10049–10057 [2] H. Tian, Z.Y. Luo, L.L. Liu, M.B. Zheng, Z. Chen, A.Q. Ma, R.J. Liang, Z.Q. Han, C.Y. Lu, and L.T. Cai. Cancer Cell Membrane-biomimetic Oxygen Nanocarrier for Breaking Hypoxia-Induced Chemoresistance. Adv. Funct. Mater, 27 (2017) 1703197. [3] G.J. Deng, Z.H. Sun, S.P. Li, X.H. Peng, W.J. Li, L.H. Zhou, Y.F. Ma, P. Gong, L.T. Cai. Cell- Membranes Immunotherapy Based on Natural Killer Cell-Membranes-Coated Nanoparticles for Effective Inhibition of Primary and Abscopal Tumor Growth. ACS Nano, 12 (2018) 12096–12108. [4] Y.T. Han, H. Pan, W.J. Li, Z. Chen, A.Q. Ma, T. Yin, R.J. Liang, F.M. Chen, Y.F. Ma, Y. Jin, M.B. Zheng, B.H. Li, L.T. Cai. T Cell Membrane Mimicking Nanoparticles with Bioorthogonal Targeting and Immune Recognition for Enhanced Photothermal Therapy. Adv. Sci., 2019, in press.

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Liqin Xiong Shanghai Jiaotong University

熊丽琴博士，上海交通大学特别研究员，博士生导师。2010 年在复旦大学化学系获博士学位。 2010 年 8 月至 2012 年 7 月，美国斯坦福大学医学院分子影像中心（Molecular Imaging Program at Stanford）博士后。2012 年 8 月加入上海交通大学生物医学工程学院，主要从事多功能荧光纳米探针的研究工作，研究方向为：肿瘤分子影像，淋巴系统功能成像，棕色脂肪成像等。在 Nature Communications、Advanced Functional Materials、Biomaterials、Nanoscale、Anal Chem. 等期刊上发表学术论文 40 余篇，h-index 17，他引次数 2800 余次(web of science)，其中高被引论文 5 篇。获 2013 年上海市科委浦江人才计划项目，2016 年度上海交通大学“李兰馨青年教师奖”，2018 年上海交通大学第二届青年教师教学竞赛（自然科学应用学科组）三等奖。主讲本科生课程《分子影像学与疾病早期诊断》及研究生课程《分子影像学技术与探针》。

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127 Multi-functional polymer dots for imaging of the lymphatics, adipose, and nerves in living mice/rats Liqin Xiong

Conjugated polymer dots emerge as attractive molecular imaging nanoprobes in living animals because of their excellent optical properties including bright fluorescence intensity, excellent photostability, high emission rates, and low intrinsic cytotoxicity. Those unique capabilities render polymer dots very promising in the investigation of cancer diagnose and imaging, tumor growth monitoring, fluorescence-guided surgery and hypoxia evaluation and other biomedical applications. In our study, to combine the strengths of the high sensitivity of NIR fluorescence imaging, high spatial resolution of photoacoustic (PA) imaging, and unlimited penetration depth of MR imaging, we designed tri-modal polymer dots by the one-pot reprecipitation method and developed these polymer dots for NIR/PA/MR imaging of the lymphatics and adipose in living mice/rats as well as tumor- bearing mice. Furthermore, combined with real-time probe-based confocal laser endomicroscopy, two- photon microscopy, and light-sheet microscopy, we carried out high resolution and 3D imaging of the lymphatics and adipose tissue. Notably, the structure of nerve fiber bundles, as well as the lymphatics and adipose tissue were simultaneously visualized. Besides, immunofluorescence staining, including UCP-1(uncoupling protein-1), LYVE-1 (lymphatic vessel endothelial hyaluronan receptor 1), and MBP (myelin basic protein), were used to confirm the in vivo and ex vivo imaging results. Our study provide a novel method for investigate the relationship between the lymphatics, adipose, and nerves in cancer metastasis, development and disease models in small animals.

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Min Zhou

Zhejiang University

周民,浙江大学转化医学研究院/浙江大学医学院附属第二医院双聘研究员，恶性肿瘤预警与干预教育部重点实验室副主任，国家千人计划青年项目和浙江省千人计划入选者。本科和博士毕业于山东大学，曾在美国德克萨斯大学安德森癌症中心任博士后和讲师职位。主要研究方向包括分子影像、转化医学等，相关成果已在临床医学、药学、化学等领域发表 60 余篇论文，包括 5 篇封面论文、5 篇 ESI 高被引论文。2017、2018 连续两年获得“浙江大学十大年度学术进展提名奖”。做为项目负责人获得国家自然科学基金、国家重点研发计划等资助。

Research activities in Prof. Min Zhou's laboratory are primarily focused on three areas: the development of targeted imaging probes for noninvasive characterization of molecular events associated with tumor progression and regression; the development of new technique for real-time imaging-guided surgery; the development of novel drug-delivery systems for selective delivery of diagnostic and therapeutic agents. Molecular imaging probes used in nuclear, optical and magnetic resonance imaging modalities are designed to enhance the sensitivity and selectivity of early tumor detection, tumor-marker profiling, and the monitoring of early treatment responses. Targeted drug delivery, on the other hand, uses nanometric drug carriers to selectively deliver anticancer agents to the tumor to maximize their therapeutic efficacy and minimize their toxic side effects to the normal tissues. Their long-term goal is to apply the “seek and treat” strategy in the development of targeted imaging/therapeutic agents that will eventually be translated to the clinic to improve the management of cancer through early tumor detection and individualized therapy.

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Ming Wang Chemistry at the Institute of Chemistry

Dr. Ming Wang is Professor of Chemistry at the Institute of Chemistry, Chinese Academy of Sciences (ICCAS). He obtained his PhD in Chemistry from ICCAS and was trained as a postdoc fellow in University of Utah and Tufts University. He started his independent research in 2016, and his research interests include developing non-viral nanoparticle for CRISPR/Cas9 delivery and in vivo genome editing, and integrating synthetic protein chemistry with nanomaterials for targeted cancer nanomedicine.

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131 Biodegradable Nanoparticles for CRISPR/Cas9 Genome Editing Delivery Ming Wang

Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing China Email: [email protected]

CRISPR/Cas9 genome editing is a transforming technique that edits mammalian gene in a highly specific manner, while its biomedical and therapeutical potential is greatly challenged by the delivery of Cas9 protein and single-guide RNA(sgRNA) into cells. In this presentation, I will be talking that how we can use a combinatorial strategy to design and optimize the chemical structure of lipid nanoparticles to improve the delivery of protein and nucleic acid, with extended application of cancer therapy and CRISPR/Cas9 genome editing. We find that the integration of chemically degradable component into the lipids enables the efficient control of lipid degradation in live cells to release protein and nucleic acid, showing an significantly enhanced protein and RNA delivery, as well as improved genome editing efficiency. An optimized lipid nanoparticle formulation shows effective RNA interference and CRISPR/Cas9 genome editing in vivo, and is therefore of great potential to fasten the clinical translation of CRISPR/Cas9 genome editing technique.

References [1] X. Yang; Q. Tang; Y. Jiang; M. Zhang; M. Wang*; L. Mao*,Nanoscale ATP-Responsive Zeolitic Imidazole Framework-90 as a General Platform for Cytosolic Protein Delivery and Genome Editing J. Am. Chem. Soc., 2019, 141, 3782-3786. [2] J. Liu; J. Chang; Y. Jiang; X. Meng; T. Sun; L. Mao; Q. Xu*; M. Wang*, Fast and Efficient CRISPR/Cas9 Genome Editing In Vivo Enabled by Bioreducible Lipid and Messenger RNA Nanoparticles, Adv. Mater., 2019, DOI:10.1002/adma.201902575

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Minglin Ma Cornell University

Minglin Ma is an Associate Professor at the Biological and Environmental Engineering Department of Cornell University. He received his BS degree from Tsinghua University and PhD from MIT, both in Chemical Engineering. Prior to joining Cornell in 2013, he worked as a Lead Scientist at General Electric Global Research Center and as a postdoctoral fellow in Dr. Robert Langer’s laboratories at MIT Koch Institute. He has published over 50 papers on journals such as Science, PNAS, Nature Materials, Nature Biotechnology, Nature Immunology and Nature Communications. His current research interest is to develop advanced biomaterials for agricultural and biomedical applications. He has obtained over 10 million dollar research funding in the past 6 years, aiming to develop a cell replacement therapy for type 1 diabetes. His work has been recognized by a number of awards including American Diabetes Association Junior Faculty Award, 3M Nontenured Faculty Award, Hartwell Foundation Individual Biomedical Research Award, Cellular and Molecular Bioengineering Young Innovator Award, BMES Advanced Biomanufacturing Junior Investigator Award, the Fiber Society Distinguished Achievement Award and two Teaching Excellence awards from Cornell University.

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133 Toroidal microgels and their applications for type 1 diabetes cell replacement therapies Minglin Ma

Biological and Environmental Engineering Department, Cornell University, Ithaca NY 14850 USA Email: [email protected]

Introduction: Type 1 diabetes (T1D) is an autoimmune disease where the patients’ insulin-producing pancreatic islet cells are mistakenly destroyed by their own immune system. It affects millions of people in the world many of whom are children. The only therapy available is based on insulin injections or infusion which can keep the patients alive but unfortunately do not cure the disease or prevent many devastating diabetic effects. Replacing the missing islet cells with immunoprotected donor islets or more ideally stem cell-derived insulin producing cells has been considered as a promising, superior alternative to the imperfect and tedious insulin therapy [1]. However, before the cell replacement concept becomes a clinical reality many challenges need to be addressed including the foreign body responses against the cell encapsulation materials, the suboptimal mass transfer and cell survival, and various safety concerns especially when stem cell-derived cells are used. [2] In this talk, I will discuss our recent efforts to develop toroidal microgel-based cell delivery devices targeting some of the above-mentioned challenges. Methods: To address the foreign body response challenge, we modified a commonly used cell encapsulation material alginate with low fouling zwitterionic moieties. To improve the mass transfer, we fabricated toroidal microgels that feature a large surface-to-volume ratio. [3] Finally, to enhance the safety of the implant, we linked the toroidal microgels together into a retrievable and replaceable system by using 3D-printed chain scaffolds. [4] Results and Conclusion: The zwitterionic modifications mitigated the foreign body responses or fibrosis in mice, dogs and pigs, and enabled diabetes correction in a rat-to-mouse transplantation model for up to 200 days. Mass transfer modelling and cell culture experiments confirmed the superior transport properties of toroidal microgels relative to conventional spherical microcapsules. We demonstrated the function of the design in diabetic mice; we also showed the easy implantation and complete retrieval. In summary, the toroidal microgel design, combined with appropriate chemical modifications, may address some of the challenges that have prevented the cell replacement therapy from clinical use.

References [1] A. U. Ernst, D. T. Bowers, L. Wang, K. Shariati, M. D. Plesser, N. K. Brown, T. Mehrabyan, M. Ma, Nanotechnology in cell replacement therapies for type 1 diabetes, Adv. Drug Deliv. Rev. In Press [2] D. An, A. Chiu, J. A. Flanders, W. Song, D. Shou, Y-C. Lu, L. G. Grunnet, L. Winkel, C. Ingvorsen, N. S. Christophersen, J. J. Fels, F. W. Sand, Y. Ji, L. Qi, Y. Pardo, D. Luo, M. Silberstein, J. Fan, M. Ma, Designing a Retrievable and Scalable Cell Encapsulation Device for Potential Treatment of Type 1 Diabetes, Proc Natl Acad Sci USA 115 (2018) E263. [3] D. An, A. Warning, K. G. Yancey, C-T. Chang, V. R. Kern, A. Datta, P. H. Steen, D. Luo, M. Ma, Mass Production of Shaped Particles through Vortex Ring Freezing, Nat. Commun. 7 (2016) 12401. [4] A. U. Ernst, L. Wang, M. Ma, Interconnected toroidal hydrogels for islet encapsulation, Adv Healthcare Mater. In press.

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Nana Zhao

Beijing University

Dr. Nana Zhao is a Professor at the College of Materials Science and Engineering, Beijing University of Chemical Technology (BUCT). He obtained his PhD in College of Chemistry and Molecular Engineering from Peking University and was trained in College of Chemistry at the University of Toronto and Materials Sciences Division at Lawrence Berkeley National Laboratory as a postdoc fellow. Her research interests focus on the design, synthesis and application of versatile organic/inorganic nanohybrids. He has published over 50 publications in top journals like Chemical Reviews, Chemical Society Reviews, Advanced Materials, ACS Nano, Nano Letters, Advanced Functional Materials, Angewandte Chemie International Edition and Small with total citations of more than 1800.

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135 Versatile organic/inorganic nanohybrids as multifunctional delivery systems Nana Zhao, Fu-Jian Xu

State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Materials Science & Engineering, Beijing University of Chemical Technology, Beijing 100029 China Email: [email protected] Introduction Organic/inorganic hybrid nanoparticles (NPs) composed of polymers and inorganic NPs with favorable physical and chemical properties are promising candidates as delivery carriers. Combining both advantages, the resultant nanohybrids usually demonstrate multi-functions. More interestingly, synergistic properties could be achieved [1]. Methods We developed several facile strategies to construct organic/inorganic nanohybrids composed of polycations to realize gene delivery. Grafting-from, grafting onto, self-assembly, and wrapping approaches were all utilized for the fabrication of these nanohybrids [2-3]. Furthermore, we employed polycation/SiO2 and polycation/Au nanohybrids as model systems to investigate the morphology effect. Results The morphology of both systems is proved to affect gene delivery. Based on these results, star-shaped hollow nanohybrids were synthesized for the co-delivery of drugs and genes [4]. A series of one dimensional nanohybrids were also designed and satisfying therapeutic effects were achieved. Taking advantage of the intriguing properties of both parts, the carriers could be employed as multifunctional platforms for biomedical applications [5]. Notably, rattle-structured rough nanocapsules with in-situ- formed gold nanorod cores were fabricated for complementary gene/chemo/photothermal therapy [6]. Conclusion These results may provide new avenues to develop promising delivery systems and useful information for the application of versatile nanohybrids in biomedical areas.

References [1] N. Zhao, L. Yan, X. Zhao, X. Chen, A. Li, D. Zheng, X. Zhou, X. Dai, Fu. J. Xu, Versatile types of organic/inorganic nanohybrids: from strategic design to biomedical applications, Chem. Rev. 119 (2019) 1666–1762. [2] N. Zhao, J. Li, Y. Zhou, Y. Hu, R. Wang, Z. Ji, F. J. Xu, Hierarchical nanohybrids of gold nanorods and PGMA-based polycations for multifunctional theranostics. Adv. Funct. Mater. 26 (2016) 5848–5761. [3] Q. Zhang, C. Shen, N. Zhao, F. J. Xu, Redox-responsive and drug-embedded silica nanoparticles with unique self-destruction features for efficient gene/drug co-delivery. Adv. Funct. Mater. 27 (2017) 1606229. [4] R. Wang, N. Zhao, F. J. Xu, Hollow nanostars with photothermal gold caps and their controlled surface functionalization for complementary therapies. Adv. Funct. Mater. 27 (2017) 1700256. [5] L. Song, N. Zhao, F. J. Xu, Self-destructible polysaccharide nanocomposites with unlockable Au nanorods for high-performance photothermal therapy. Adv. Funct. Mater. 27 (2017) 1701255. [6] X. Chen, Q. Zhang, J. Li, M. Yang, N. Zhao, F. J. Xu, Rattle-structured rough nanocapsules with in-situ-formed gold nanorod cores for complementary gene/chemo/photothermal therapy. ACS Nano 12 (2018) 5646–5656.

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Peng Huang Shenzhen University

Dr. Peng Huang is a Distinguished Professor, Director of Department of Molecular Imaging, Chief of Laboratory of Evolutionary Theranostics, at the School of Biomedical Engineering, Shenzhen University, China. His research is focused on the design, synthesis, and biomedical applications of multifunctional nanomaterials. He has published over 150 peer-reviewed papers in reputed international journals such as Nature Biomedical Engineering (1), Chemical Reviews (1), Chemical Society Reviews (6), Accounts of Chemical Research (1), Advanced Materials (13), Angewandte Chemie International Edition (3), Journal of the American Chemical Society (2), Nano Letters (2), ACS Nano (9), Materials Horizons (2), Progress in Polymer Science (1), Advanced Drug Delivery Reviews (1), Biomaterials (11), and Small (7). Among them, fifteen papers were listed as 1%ESI highly cited papers. His publications have received a total citation of > 10,000 times and given him an H-index at 56.

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137 Glucose Oxidase-based cancer therapy

Peng Huang*

Marshall Laboratory of Biomedical Engineering, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, China Email: [email protected]

Glucose oxidase (GOx) with fascinating catalytic property has aroused considerable interest in cancer therapy through the oxidation of glucose into gluconic acid and hydrogen peroxide (H2O2). These two products could induce the chain reaction for synergistic cancer therapy by combining direct depletion of intratumoral glucose (known as cancer starvation therapy) with other therapeutic approaches. In the past five years, we have explored a series of nanoplatforms using GOx as the building block for starvation-based synergistic therapy of cancer. This talk will highlight our recent advances in the development of GOx-based nanomedicines in this cutting-edge research area. Some issues of GOx-based nanomedicines in the clinical translation will also be discussed.

References [1] L.-H. Fu, C. Qi, Y.-R. Hu, J. Lin, P. Huang,* Glucose oxidase-instructed multimodal synergistic cancer therapy. Adv. Mater. 31 (2019) 1808325. [2] Y. Zhang, Y. Yang, S. Jiang, F. Li, J. Lin, T. Wang, P. Huang,* Degradable silver-based nanoplatform for synergistic cancer starving-like/metal ion therapy, Mater. Horiz. 6 (2019) 169– 175. [3] L.-H. Fu, C. Qi, J. Lin, P. Huang,* Catalytic chemistry of glucose oxidase in cancer diagnosis and treatment. Chem. Soc. Rev. 47 (2018) 6454–6472. [4] W. Fan, B. Yung, P. Huang,* X. Chen,* Nanotechnology for multimodal synergistic cancer therapy. Chem. Rev. 117 (2017) 13566–13638. [5] W. Fan, N. Lu, P. Huang,* Y. Liu, Z. Yang, S. Wang, G. Yu, Y. Liu, J. Hu, Q. He, J. Qu, T. Wang,* X. Chen,* Glucose-responsive sequential generation of hydrogen peroxide and nitric oxide for synergistic cancer starving-like/gas therapy. Angew. Chem. Int. Ed. 56 (2017) 1229– 1233.

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Mi Peng Sichuan University

Peng Mi is a professor at the Department of Radiology, Center for Medical Imaging, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China. He received his Ph.D. from The University of Tokyo in 2013 under the supervision of Prof. K. Kataoka. After a JSPS postdoctoral fellowship at the Tokyo Institute of Technology until 2015, he joined the Innovation Center of Nanomedicine in Kawasaki as a senior research scientist until 2016. His major research interests relate to biomaterials and nanodevices for precision diagnosis, drug delivery and targeted therapy.

Albumin nanoparticles for precision MR imaging of acute myocardial infarction in rabbit models Peng Mi, Fang Wang

Department of Radiology, Center for Medical Imaging, and State Key Laboratory of

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139 Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China Email: [email protected]

It is important to diagnosis of acute myocardial infarction at the early stage due to its severe mortality and morbidity. Here, in this study, the albumin

nanocomposites with MnO2/Gd2O3 motifs

(MnO2@BSA and Gd2O3@BSA) have been engineered through the biomineralization approach for T1- Figure 1. Schematic illustration of Gd2O3@BSA and weighted MR imaging of myocardial MnO2@BSA nanoparticles for MR imaging of AMI in infarction. The nanocomposites were rabbit models, as the nanoparticles could accumulated approximately 20-30 nm in diameter with

in myocardial infarction regions for specific contrast spheroid morphology. The Gd2O3@BSA enhancement. were stable in normal physiological conditions (pH 7.4) and acidic myocardial infarction regions with almost steady -1 -1 molecular relaxivity approximately 10 mM s . Meanwhile, the MnO2@BSA have exhibited pH- triggered releasing of Mn2+ at the acidic myocardial infarction microenvironments, and exhibited low molecular relaxivity (0.34 mM-1s-1) at normal physiological conditions (pH 7.4) and 38-fold (13.08 mM-1s-1) increased relaxivity at the acidic myocardial infarction microenvironments. Furthermore, the

MnO2@BSA and Gd2O3@BSA have demonstrated high accumulation in the acute myocardial infarction regions at 1 and 12 h post i.v. injection respectively, accounting high contrast enhancement for MR imaging of acute myocardial infarction in rabbit models.

References [1] B.L. van der Hoeven, M.J. Schalij, V. Delgado, Multimodality imaging in interventional cardiology, Nat. Rev. Cardiol. 9 (2012) 333-346. [2] G. de Couto, M. Ouzounian, P.P. Liu, Early detection of myocardial dysfunction and heart failure, Nat. Rev. Cardiol. 7 (2010) 334-344. [3] P. Mi, D. Kokuryo, H. Cabral, H. Wu, Y. Terada, T. Saga, I. Aoki, N. Nishiyama, K. Kataoka, A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy, Nat. Nanotechnol. 11 (2016) 724-730.

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Pengcheng Zhang Shanghai Institute of Materia Medical

Pengcheng Zhang got his PhD at Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences in 2011, and then conducted his post-doctoral research on peptide self-assembly at the Johns Hopkins University. He returned to SIMM in 2014, and is now a professor there. His research interests mainly focus on the development of nanomedicines using self-assembling and biomimetic strategies.

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141 Combined photochemotherapy using co-delivery nanomedicine to overcome intratumoral heterogeneity Pengcheng Zhang, Yihui Zhai, Qingshuo Meng, Jia Meng, Yaping Li

Center of Pharmaceutics & State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 Email: [email protected]

Intratumoral heterogeneity is an inherency of triple-negative breast cancer (TNBC), which hinders effective chemotherapy of the disease. Combined therapies superior to monotherapy presumably by addressing intratumoral heterogeneity, but their clinical application is limited by greater toxicity. Combined phototherapy and chemotherapy with nanomedicine may be advantageous, as the two complemented each other in their patterns and mechanisms of action. However, further understanding of the interaction between the photosensitizer (PS) and anti-cancer drugs is necessary to maximize the synergistic effect. The photochemical interaction between PS and anti-cancer drugs and its influence on their anti-cancer activity were first explored. Optimized co-delivery nanomedicines were then created, and their interaction with and efficacy against cancer cells and orthotopic TNBC tumors were investigated, with a special focus on the mechanism of synergistic action. We found that 1 the singlet oxygen ( O2) generated by PS could react with drugs containing alky-, phenol-, or indole- group to form inactive peroxide. To avoid the chemical antagonism, the anti-drugs should be either 1 1 inert to O2 or isolated from PS. Based on this finding, methylene blue and O2-inert cisplatin were encapsulated into a biomimetic nanovesicle (MPV) with a cell membrane–derived shell and a gelatin nanogel core to overcome the heterogenous drug distribution in the TNBC tumor. Upon laser irradiation, the MPV first produced hyperthermia that enhanced intratumoral drug penetration, and 1 then generated O2 to facilitate the cytosol deposition and potentiate activity of methylene blue and cisplatin via breaking down plasma membrane. In addition to heterogenous drug distribution, we also created a co-delivery nanomedicine to address the periphery-core heterogeneity of TNBC tumors. In mice bearing 4T1 tumors, fast growing tumor cells in the periphery were killed by photodynamic therapy (PDT), where the irradiation intensity was strong. In the core of the tumor, the PDT was insufficient to kill cancer cells due to significant attenuation of the laser, but was able to potentiate chemotherapy and gene therapy by facilitating the endosomal escape of paclitaxel and anti-Twist siRNA. Both co-delivery nanomedicine retarded the growth of primary tumor and inhibited the pulmonary metastasis of TNBC without significant toxicity. Our findings reveal the mechanisms that lead to antagonism and synergism between PDT and chemotherapy, and demonstrate the potential of combine phototherapy and chemotherapy in addressing intratumoral heterogeneity.

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Qiang Zhang Peking University

Dr. Qiang Zhang received his Bachelor’s degree in Beijing Medical College in 1982 and received his Ph.D degree at West China University of Medical Sciences in 1995. After working in Sichuan Industrial Institute of Antibiotics for 10 years, in 1995 he moved to School of Pharm. Sci., Peking University where he was promoted to Associated Professor in 1996 and Professor in 1999. He began his study in nanomedicine in 1992 when reading for Ph.D degree. Now more than 300 SCI papers were published, which was highly cited, garnered numerous awards, and boosted related pharmaceutics research. As the DDS people, he have developed serial DDS into market and some others into clinical study. One of them has become the star product of a major domestic pharmaceutical company, having brought in significant economic and social benefits. Currently he is the Honor Chair of Pharmaceutics Committee of Chinese Pharmaceutical Association (CPA), Founder and Vice-Chair of Nanomedicines Committee of CPA, Vice-Chair of Pharmaceutics Committee of Chinese Pharmacopoeia, Expert for Center of Drug Evaluation of CFDA, the first Editorial board member of J Controlled Release in China, and so on. He was also the first President of CRS-China Chapter and the Vice-Dean of School of Pharm. Sci., Peking University. Research Interests: Molecular Pharmaceutics and the translational study on novel DDS, including the mechanism and translational studies on novel drug delivery systems for water-insoluble drugs, antitumor drugs and biotechnology drugs.

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143 Cellular Trafficking and Bioresponse of Nanomedicines Bing He, Hua Zhang, Wenbin Dai, Xueqing Wang, Qiang Zhang,*

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.

Background. Overcoming the epithelial barriers to enhance drug transport is a focused topic for gastrointestinal, intratracheal, intranasal, vaginal and intrauterine delivery. Nanomedicines with targeting functionization promote such a process owing to specific ligand-receptor interaction. However, compared to the cell uptake of targeting nano-therapies, currently few studies concentrate on their transcytosis including endocytosis for ‘in’ and exocytosis for ‘out’. In fact, the cellular regulatory mechanism for these pathways, as well as the principle of ligand’s effect on the transcytosis, are almost ignorant. Methods. Given the intracellular stability and detectability, the canonical gold nanogranules (GNG) were fabricated as the models of nanomedicines, and then modified with transferrin (Tf) as the well- established targeting ligand (Tf-NG). Bovine serum albumin modified nanogranules (BSA-NG) were prepared as the non-specific reference. Caco-2 and MDCK cells as the most frequently used epithelium were chosen as cell models thanks to their naturally difference in transferrin receptor polarity or distribution. The whole study was focused on the comparison between Tf-NG and BSA-NG in two cell models. Besides other technologies, confocal laser scanning microscopy (CLSM) based on laser reflection (LR) was applied to investigate the trafficking pathway of Tf-NG, after the polarity evaluation of Tf receptor (TfR). Quantitative proteomics, a powerful high-throughput technology, was utilized to study the cellular response in terms of protein expression, followed by bioinformatical analysis based on big data. Results Compared to the non-specific reference, Tf-conjugation boosted the endocytosis by different pathways in two cell models, and transformed the intracellular route of Tf-NG in both cells differently, affecting exocytosis, recycling, degradation but not secretion pathway. Only bipolar cells could establish a complete transport flow from ‘in’ to ‘out’, leading to the enhanced transcytosis of Tf-NG. Importantly, epithelia could make responses to Tf-NG transcytosis. Based on the quantitative proteomics, the intracellular trafficking of Tf-NG altered the protein expression profiles, in which the endocytosis- and transcytosis-related proteins were specifically upregulated. Particularly, only bipolar cells could positively feed back to such trafficking via accelerating the subsequent Tf-NG transcytosis. Here, all the cell transport of Tf-NG was polarity-associated.. Conclusions Tf-modification elevated the transcytosis of Tf-NG across epithelium by triggering polarity-associated transport flow and positive cell feedback loop. These findings provided an insight to the targeting nano-delivery for efficient transport through epithelial barriers.

Reference [1] Suxin Li, Qiang Zhang, et al. Novel Biological Functions of ZIF-NP as a Delivery Vehicle: High Pulmonary Accumulation, Favorable Biocompatibility, and Improved Therapeutic Outcome, Advanced Functional Materials. 26(2016)16: 2715-2727 [2] Yanan Sun, Qiang Zhang, et al. A Peptide-Drug Conjugate Based Nanocombination Actualizes Breast Cancer Treatment by Maytansinoid/ Photothermia with Assistance of Fluorescent/Photoacoustic Images, Nano Letter, 2019, online. [3] Dan Yang, Qiang Zhang, et al. Transferrin Functionization Elevates Transcytosis of Nanogranules across Epithelium by Triggering Polarity-Associated Transport Flow and Positive Cellular Feedback Loop, ACS Nano. 2019, online.

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Qigang Wang Tongji University School of Chemical Scicence and Engineering, Shanghai 200092, China Phone/Fax: (+86)-21-6598-9301 E-mail: [email protected]

Research interests: Enzymatic polymerization; Biological oxidation; Confinement effect of hydrogel; Cancer Therapy; Tissue engineering

Biographic description: Dr. Qigang Wang received his bachelor’s degree in 1999 and Master’s degree (Supervisor: Prof. Jinsheng Gao) in 2002 from East China University of Science and Technology. He then obtained his Ph.D. in 2005 from Shanghai Institute of Ceramics, Chinese Academy of Sciences (Supervisor: Prof. Qiuming Gao). He was the postdoctor at the Hong Kong University of Science and Technology from 2005-2007 (Supervisor: Prof. Bing Xu). He continued the postdoctor trainning at The University of Tokyo and Riken from 2005 to 2011 (Supervisor: Prof. Takuzo Aida). He is a currently a professor in the School of Chemical Science and Engineering, Tongji University.

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145 Regulatable blocatalysis of enzyme-laden nanogels for photothermal- biological cascade antitumor therapy Xiaoshan Wang, Xia Wang* and Qigang Wang*

School of Chemical Science and Engineering, Tongji University, Shanghai 200092, China Email: [email protected]

Bio-oxidation is an important process for life. Currently, the enzyme related bio-oxidative have been taken as an adjunctive theraputic way for anticancer treatment as biocatalyst by imitating process of the innate immune system combating infections and bacterials in our group [1-2]. However, the bio- oxidative strategies for directly cancer therapy are far from enough and still be challenging. Actually, in our innate immune systems, marvelous neutrophils can be activated precisely by the firstly inflammatory stimulation and thereafter secrete oxidative enzymes to upregulate the ROS level via a biocatalysis pathway. Therefore, in this work, as a proof-of-concept study, we engineer a novel kind of enzyme-loaded gold rod-based nanogel system as the regulatable photothermal effects for physical stimulation and thus induced biocatalysis for synergistic antitumor therapy. By using gold nanorods

(Au NRs) as the core, the oligopeptide gel factor (Fmoc-Tyr(H2PO3)-OH) was self-assembled to the supramolecular hydrogel layers around by the hydrolysis of acid phosphatase (AP). The bio-enzyme- loaded gold rod-based nanogel (Au NRs-SNgel@CPO) can be therefore finally achieved by loading the theraputic chloroperoxidase (CPO) in the nanogel layers. The morphology and structure of Au NRs-SNgel@CPO were characterized by various instruments, indicating that the material has good dispersity, with the size about 45×15 nm and an obvious core-shell structure. Further, the synergistic therapeutic effect was investigated both by intratumoral injection and intravenous injection on the tumor-bearing mouse model. The results showed that Au NRs-SNgel@CPO can effectively inhibit tumor growth and can be used as a new and effective photothermal-enzyme dynamic agent for synergistic tumor treatment.

References [1] Q. Wu, Z.G. He, X. Wang,* Q. Zhang, Q.C. Wei, S.Q. Ma, C. Ma, J.Y. Li,* Q.G. Wang,* Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy, Nat. Commun. 10 (2019) 240. [2] Q.C. Wei, S. Jiang, R.R. Zhu, X. Wang, S.L. Wang,* Q.G. Wang,* Injectable Peptide Hydrogel Enables Integrated Tandem Enzymes’ Superactivity for Cancer Therapy, iScience 14 (2019) 27-35.

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Qingsong Yu Beijing University

Dr. Qingsong Yu is now an Associate Professor at the College of Life Science and Technology, Beijing University of Chemical Technology (BUCT). He obtained his Bachelor in Biomaterials from BUCT and his PhD in Polymer Chemistry and Physics from Institute of Chemistry, Chinese Academy of Sciences. He was then trained in BUCT as a postdoc fellow. His research interests span across the design and development of novel polymeric anticancer nanomedicines, the fundamental understanding of the in vivo transportation processes and the biological effects of these nanomedicines. He also focused on the clinical translational research of nanomedicine. He has published over 15 publications over his scientific career, in scientific journals like Journal of Controlled Release, ACS Applied Materials & Interfaces, Biomacromolecules.

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147 Prodrug nanomedicine for efficient concurrent chemoradiotherpy Kejun Luo, Keqi Xiang, Qingsong Yu*, Zhihua Gan

State Key Laboratory of Organic-Inorganic Composite Materials, Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, China, 100029 E-mail address: [email protected]

Radiotherapy is utilized as primary or adjuvant treatment against many cancers. Multimodal treatment, such as concurrent chemoradiotherapy, has been used to improve the antitumor effects of radiation.[1] An effcient radiosensitizer is defined as an agent that induces minimum intrinsic toxicity while demonstrating additive or supra-additive effects with radiation without causing a significant increase in radiotoxicity.[2] However, most agents currently used in the clinic for radiosensitization are toxic. The development of nanotechnology has brought traditional chemotherapeutics safety and efficacy improvements.[3] However, the emergence of chemoradio-resistance still limited the applications these nanomedicines. Herein, in order to enhance the toxicity profiles of traditional chemotherapeutics and to overcome the chemoradio-resistance of cancer cells, we developed a series of tumor microenvironment responsive prodrugs with chemotherapeutics such as gambogic acid, cisplatin, doxorubicin and a typical radiosensitizer, metronidazole. Block copolymers containing both polyethylene glycol and metronidazole was also synthesized to efficiently encapsulate the above prodrugs. Due to the enhanced permeability and retention effect of nanostructures, these prodrug nanomedicines exhibited excellent tumor accumulation. Moreover, the radiosensitization effect of chemotherapeutics could be attenuated in the normoxic region such as normal organs while be amplified in hypoxic regions like solid tumors due to the presence of metronidazole in the prodrugs. Therefore, the toxicity and efficacy profiles of the parent drug could be better optimized so that supra-additive effects could be observed for these prodrug nanomedicines. It could also be found that, in some cases, these prodrug strategies offer valuable options to overcome the chemoradio-resistance of their parent drugs. This could be explained in two aspects, one is that the nano-formulation might alter the intracellular transportation pathways of the parent drugs,[4] the other is that the multi-target effect of metronidazole might consolidate the DNA damage caused by radiation and chemotherapeutics.[5] As a result, the ease of fabrication, the ultra-high drug loading capacity and the remarkable synergistic effect endowed as-reported prodrug nanomedicines with great potential in the further clinical application.

Acknowledgements: This work was financially supported by the National Natural Science Foundation of China (Nos. 51503013, 51390481, 21774008, and 81472412). This work was also supported by the Fundamental Research Funds for the Central Universities of China (No. XK1701, XK1802-8) and Research projects on biomedical translation of China-Japan Friendship Hospital (No. PYBZ1823, PYBZ1838).

References [1] T.Y. Seiwert, J.K. Salama, E.E. Vokes, The concurrent chemoradiation paradigm—general principles, Nat. Clin. Pract. Oncol., 4 (2007) 86. [2] B.B. Ma, R.G. Bristow, J. Kim, L.L. Siu, Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents, J. Clin. Oncol., 21 (2003) 2760-2776. [3] W. Ngwa, R. Kumar, M. Moreau, R. Dabney, A. Herman, Nanoparticle drones to target lung cancer with radiosensitizers and cannabinoids, Frontiers in Oncol., 7 (2017) 208. [4] K.W. Kang, M.-K. Chun, O. Kim, R.K. Subedi, S.-G. Ahn, J.-H. Yoon, H.-K. Choi, Doxorubicin- loaded solid lipid nanoparticles to overcome multidrug resistance in cancer therapy, Nanomed.: Nanotechnol., Biol. and Med., 6 (2010) 210-213. [5] M. Nordsmark, J. Alsner, M. Busk, J. Overgaard, M.R. Horsman, Hypoxia and radiation therapy, in: Hypoxia and Cancer, Springer, 2014, 265-281.

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Selena Xu

FUJIFilm VisualSonics Inc.

Dr Xu graduated with Ph.D from Shanghai Institute of Biochemistry and Cell Biology, Chinese Acadamy of Sciences. After graduation, she has been working in the promotion of molecular imaging technology for over ten years. She is farmiliar with the applications of many molecular imaging methods such as micro-US, PA, Optical imaging, micro-MRI and micro-CT, etc. She has unique views on how to use micro-ultrasound, photoacoustic imaging and multi-modal imaging technology in scientific research.

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Shaobing Zhou Southwest Jiaotong University

Dr. Shaobing Zhou is currently a full professor in the School of Materials Science and Engineering at Southwest Jiaotong University. He was awarded the National Science Fund for Distinguished Young Scientists of China in 2017. His research interests include drug controlled release system and tissue engineering scaffold. He is the author or coauthor of more than 120 refereed articles and 25 Chinese patents/patent applications. He has been cited over 5500 times and has an h-index of 45.

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151 A multifunctional lipid-polymer hybrid vesicle for improving tumor therapy Huili Sun1,2, Jianwen Hou2, Shaobing Zhou1,2 *

1 School of Life Science and Engineering Southwest Jiaotong University, Chengdu 610031, P.R. China. E-mail: [email protected]; [email protected] 2 Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering Southwest Jiaotong University, Chengdu 610031, P.R. China

In the last few decades, liposome has played a very important role in constructing smart therapeutic delivery nanosystems for cancer therapy [1]. However, some major drawbacks associated with liposomes, such as poor storage stability and low Fig. 1. TEM image (a) and schematic illustration (b) of encapsulation efficiency, severely lipid–polymer hybrid nanovesicles loaded with hydrophilic restrict their application for cancer and hydrophobic therapeutic agents; (c) The tumor weights treatment. Compared to liposomes, of the mice bearing MCF-7 cell in situ after treated with polymeric nanoparticles exhibit better hybrid NVs and saline at day 19. Statistics analysis: *** stability during storage, superior p < 0.001 vs. control group. structural integrity and controlled release capability [2]. So polymeric nanoparticles are perceived as an ideal drug delivery vehicle to address the limitations of liposomes. In this study, we have developed a multifunctional lipid-polymer hybrid nanovesicle (Hybrid NV) composed of phenylboronic acid-polyethylene glycol-disulfide bond‐poly(ε‐caprolactone) (PBA-PEG- ss-PCL) and phospholipid, to simultaneously co-deliver hydrophobic and hydrophilic therapeutic agents for improving the efficacy of cancer treatment. And rapid release of hydrophobic therapeutic agent in the lipid bilayer and sustained release of hydrophilic therapeutic agent in the aqueous core can be achieved. Hybrid NVs have a significantly prolonged circulation half-life and ligands conjugated on polymers can increase the cellular uptake of therapeutic agents by cancer cells. In vitro cell experiments show that Hybrid NVs exhibit higher cytotoxicity to MCF-7 cell lines, and in vivo studies show that more hybrid NVs are accumulated at tumor sites and generate better antitumor effects compared with the control group (saline group) (Fig. 1). In conclusion, the lipid-polymer hybrid nanocarriers simultaneously delivering hydrophobic and hydrophilic therapeutic agents may provide an advanced drug delivery technology for improving the chemotherapeutic efficacy.

References [1] S. Deshpande, F. Brandenburg, A. Lau, M.G.F. Last, W.K. Spoelstra, L. Reese, S. Wunnava, M. Dogterom, C. Dekker, Spatiotemporal control of coacervate formation within liposomes, Nat. Commun. 10 (2019) 1800. [2] T. Date, V. Nimbalkar, J. Kamat, A. Mittal, R.I. Mahato, D. Chitkara, Lipid-polymer hybrid nanocarriers for delivering cancer therapeutics, J. Control. Release 271 (2018) 60-73.

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Shaoqin Sarah Gong University of Wisconsin–Madison

She received her BA and MS degrees from Tsinghua University and her PhD degree from the University of Michigan–Ann Arbor—all in Materials Science and Engineering. Currently, Dr. Gong’s research focuses on the design, synthesis/fabrication, and characterization of novel nanomaterials and biomaterials for various biomedical applications. Dr. Gong is a fellow of the American Institute for Medical and Biological Engineering. She has co-authored over 160 peer-reviewed journal articles and 140 conference papers and is a co-inventor of 20 issued/pending US patents. She is an editorial board member for several journals including Biomaterials, Theranostics, Biofabrication, and Nanotheranostics and served as an Associate Editor for Biomaterials. Dr. Gong is a winner of a number of awards including the NSF CAREER Award and NIH Faculty Career Development Award. She is also a member of the Board of Directors for the Chinese American Society of Nanomedicine and Nanobiotechnology.

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153 Non-Viral Nanoplatforms for the Delivery of CRISPR Genome Editing Machineries

Shaoqin Sarah Gong1,2, 3, 4 *, Yuyuan Wang2, 4, Guojun Chen2, 4, Amr Abdeen2, Pawan K. Shahi5, Samantha Robertson6, Ruosen Xie1, 2, Masatoshi Suzuki1,6 Bikash R. Pattnaik5,7 Ruosen Xie2, 4, Krishanu Saha1, 2 1Department of Biomedical Engineering, 2Wisconsin Instittute for Discovery, University of Wisconsin-Madison. 3Department of Chemistry, University of Wisconsin-Madison. 4Department of Materials Science and Engineering, University of Wisconsin–Madison. 5Department of Pediatrics, University of Wisconsin-Madison. 6 Department of Comparative Biosciences, University of Wisconsin-Madison. 7Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison. *Email: [email protected]

CRISPR/Cas9 is a revolutionary and versatile genome editing technique with wide-ranging utility [1]. However, to date, successful genome editing has mostly been done using viral vectors that require laborious customization and have troublesome safety profiles [2]. Thus, there is an urgent need to develop efficient non-viral delivery vehicles for safe in vivo CRISPR/Cas9 genome editing. One attractive strategy is to deliver preassembled Cas9-gRNA ribonucleoproteins (RNPs). RNPs, readily scaled up at an industrial level with high quality assurance, are effective but short lived; thus significantly diminishing the off-target effect [3]. In this talk, I will present two types of non-viral nanoplatforms recently developed by my laboratory in collaboration with several other research laboratories at the University of WisconsinMadison. These stimuli-responsive nanoplatforms can deliver either RNP or RNP together with DNA repair template (e.g., ssODN) and enable efficient gene disruption or gene repair in vitro and in vivo. Figure 1: (a) Sp.Cas9 has a heterogeneous surface charge due to both positive and negative amino acid residues, as well as its negatively charged sgRNA. A schematic illustration of the formation of the covalently- crosslinked, yet intracellularly biodegradable, nanoca¬psule (NC) for the delivery of the Cas9 RNP complex prepared by in situ free radical polymerization. (b) A schematic depiction of the proposed mechanism of the cellular uptake of NCs and the subcellular release of RNP.

References [1] Sander, J.D. and J.K. Joung, CRISPR-Cas systems for editing, regulating and targeting genomes. Nature biotechnology, 2014. 32(4): p. 347-355. [2] Miller, J.B., et al., Non‐Viral CRISPR/Cas Gene Editing In Vitro and In Vivo Enabled by Synthetic Nanoparticle Co‐Delivery of Cas9 mRNA and sgRNA. Angewandte Chemie International Edition, 2016. [3] Liang, X., et al., Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection. Journal of biotechnology, 2015. 208: p. 44-53.

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Shaoyi Jiang University of Washington

Biomolecular Interfaces and Biomaterials Molecular Understanding, Design and Development of Zwitterionic-based Functional Materials An important challenge in many applications ranging from biomedical devices to ship hulls is the prevention of nonspecific biomolecule and microorganism attachment onto surfaces. This attachment can be prevented by using a "nonfouling" surface. Their goals are to provide a fundamental understanding of molecular-level nonfouling mechanisms and to develop biocompatible and environmentally benign nonfouling materials using molecular design principles. Over the last few years, they have demonstrated that zwitterionic and mixed charge materials are unique, effective and robust for a wide range of applications. In addition to their excellent nonfouling properties, zwitterionic carboxybetaine-based materials have abundant functional groups for ligand immobilization. Superhydrophilic zwitterionic materials maintain protein and cell bioactivity while inducing no capsule formation around tissues and no immunological response in blood circulation. Cationic and hydrolysable zwitterionic ester precursors have self-sterilizing capabilities and other unique properties. their results show that the strong hydration of zwitterionic materials is responsible for their excellent nonfouling properties. they take a unique holistic approach to our research by performing both simulations and experiments. Novel materials are designed, synthesized, tested and improved upon all within our group. This collaborative approach allows us to always strive towards understanding nature at all levels. Creative ideas and innovative technologies are always their emphasis.

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155 Zwitterionic Materials for Nanomedicine Applications Shaoyi Jiang

Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA Email: [email protected]

An important challenge in many biomedical applications is the prevention of nonspecific protein adsorption on surfaces. At present, there are few materials that can effectively resist nonspecific protein adsorption or microorganism attachment from complex media and meet the challenges of practical applications. Poly(ethylene glycol) (PEG) has been the benchmark of stealth materials. However, PEG is susceptible to oxidation damage. Moreover, the potential of PEG in eliciting immune responses raises serious concerns about its safety. Extensive research is underway to develop new stealth materials in an effort to address the limitations of PEG. Over years, we have demonstrated several ultra-low fouling zwitterionic materials such as poly(carboxybetaine) (pCB), poly(sulfobetaine) (pSB) and poly(trimethylamine-N-oxide) (PTMAO) [1,2]. At present, advances in protein therapy are hindered by the poor stability, inadequate pharmacokinetic (PK) profiles, and immunogenicity of many therapeutic proteins. PEG conjugation or PEGylation is the most successful strategy to date to overcome these shortcomings, and more than 10 PEGylated proteins have been brought to market. However, induced and pre-existing anti-PEG antibodies raise serious concerns about the future of PEGylated therapeutics. Here, we demonstrate new protein conjugation technologies based on zwitterionic PCB or PTMAO polymers (or Zwitterlation) in the forms of conjugates or nanogels. PCB and PTMAO polymers are both derived from naturally occurring glycine betaine and trimethylamine-N-oxide, which are used as proteins stabilizer. While PEG is amphiphilic with both hydrophilic and hydrophobic characteristics, both PCB and PTMAO polymers are superhydrophilic and are invisible in complex media. Results show that PCB or PTMAO protein encapsulation methods effectively enhance protein stability, PK and pharmacodynamics (PD) while mitigating the immune response [3,4]. Several immunogenic proteins are compared. While anti-PEG antibodies were observed, no antibodies against PCB or PTMAO polymers were detected for all of these studies after 3-5 weekly injections in a rat model. We also demonstrate a PCB-protected bioscavenger that offers long-term protection against organophosphates (OP) intoxication in guinea pigs [5]. The proposed technologies are applicable to a variety of proteins and unlocks the possibility of adopting highly immunogenic proteins for therapeutic or protective applications. In addition to proteins, these technologies have also been demonstrated to have superior performance over PEGylation for micelles, liposomes, nanogels and solid nanoparticles (e.g., iron oxides, gold, silica and quantum dots) for nanomedicine and nanodiagnostics.

References [1] S. Jiang and Z. Q. Cao, Ultralow-Fouling, Functionalizable, and Hydrolyzable Zwitterionic Materials and Their Derivatives for Biological Applications, Advanced Materials, 22, 920 (2010). [2] A. Keefe, S. Jiang, Poly(zwitterionic) protein Conjugates Offer Increased Stability without Sacrificing Binding Affinity or Bioactivity, Nature Chemistry, 4 (2012) 59. [3] P. Zhang, F, Sun, C. Tsao, S. Liu, P. Jain, H.C. Hung, T. Bai, K. Wu, S. Jiang, Zwitterionic encapsulation promotes protein stability, enhances pharmacokinetics and reduce immune response, Proceedings of the National Academy of Sciences, 112 (2015) 12046. [4] P. Zhang, E.J. Liu, C. Tsao, S.A. Kasten, M. V. Boeri, T. L. Dao, S. J. DeBus, C. Linn Cadieux, T.C. Otto, D. M. Cerasoli, Y. Chen, P. Jain, F. Sun, W. Li, H-C. Hung, Z. Yuan, J. Ma, N. Bigley, F M. Raushel and S Jiang, Nanoscavenger Provides Long-term Prophylactic Protection against Nerve Agents, Science Translational Medicine, 11, aau7091 (2019). [5] B. Li, P. Jain, J. Ma, J.K. Smith, Z. Yuan, H.-C. Hung, Y. He, X. Lin, K. Wu, J. Pfaendtner, S. Jiang, Trimethylamine N-oxide Derived Zwitterionic Polymers: A New Class of Ultra-low Fouling Bioinspired Materials, Science Advances, Vol. 5, no. 6, eaaw9562 (2019).

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Shiyong Liu University of Science and Technology of China

Shiyong Liu obtained his B. S. degree in 1993 and M. S. degree in 1996 from Wuhan University, majoring in environmental chemistry and polymer chemistry, respectively. After obtaining his Ph.D. degree in 2000 at Fudan University with Prof. Ming Jiang, he spent three and a half years at University of Sussex and University of Delaware as a postdoctoral fellow, working with Prof. Steven P. Armes (currently at University of Sheffield) and Prof. Eric Kaler (currently at University of Minnesota, respectively. Since 2004, he has been a professor of Polymer Science and Engineering at the University of Science and Technology of China. His current research interests include precision polymers, digitalized assemblies of sequence-controlled polymers, peptide assemblies, supramolecular chirality, synthetic polypeptide chemistry, protein coronas, and contrast agents for medical diagnosis. He has served as Associate Editors for Chem. Mater. (ACS) and Chinese J. Polym. Sci. journals.

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157 Sequence-Controlled Polymers for Direct MALDI-TOF MS Reading and Quantification of NP Biodistribution Shiyong Liu

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158

Shutao Guo Nankai University

Dr. Shutao Guo is a Professor of Polymer Chemistry at Nankai University since 2017. He obtained his B.S in Chemical Engineering and Technology from Tianjin University in 2006 and Ph.D in Materials Science and Engineering from Tianjin University in 2010. Dr. Guo did postdoctoral training with Prof. Leaf Huang at University of North Carolina at Chapel Hill (2011-2014), and Prof. Robert Langer and Prof. Daniel Kohane at Massachusetts Institute of Technology/Harvard Medical School (2014-2017). He has published more than 40 articles in Journal of the American Chemical Society, ACS Nano, Advanced Functional Materials, Biomaterials, etc.

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159 Ketal-based Drug Conjugates and Biomaterials Haiping Zhong, Yang Xu, Na Yu, Tao Liu, Shutao Guo*

Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China *Email: [email protected]

Ketals, which are degradable and have tunable pH-sensitivity, are very useful in pH-responsive drug delivery systems and biomaterials. In this presentation, a facile approach to synthesis of polyketals and its use to synthesize drug-polyketal conjugates will be introduced. Particulate formulations of drug-polyketal conjugates have shown great potential in drug delivery and controlled release. Our latest advances in using ketal linkages to construct pH-sensitive prodrugs will be also presented.

References 1. Binauld, S.; Stenzel, M.H., Acid-Degradable Polymers for Drug Delivery: A Decade of Innovation. Chem. Commun. 2013, 49 (21), 2082-2102. 2. Guo, S.; Nakagawa, Y.; Barhoumi, A.; Wang, W.; Zhan, C.; Tong, R.; Santamaria, C.; Kohane, D. S., Extended Release of Native Drug Conjugated in Polyketal Microparticles. J. Am. Chem. Soc. 2016, 138 (19), 6127-6130.

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Tianfeng Chen Jinan University and The First Afﬁliated Hospital

Dr. Tianfeng Chen is Professor at the Department of Chemistry, Jinan University and The First Afﬁliated Hospital. He obtained his PhD in Chemical Biology and was trained as postdoc fellow in The Chinese University of Hong Kong. He dedicates himself to the design and synthesis of potential cancer-targeting drug delivery systems and molecules based on the biochemical characteristics of cancer cells and the microenvironments. Collectively, these researches have been supported by several grants, including National High-level personnel of special support program, 863 National High Technology Research and Development Program of China and Natural Science Foundation of China and Program. The research efforts have been disseminated in excess of 150 scientific papers in journals like Adv Funct Mater, Angew Chem Int Ed, ACS Nano and Biomaterials, 50 China and USA patents. He has a h-index of 50 with total citations of more than 5000. His research has won the 2018 Chinese Medical Science and Technology Award and 2018 Guangdong Natural Science second Award as the first complete adult.

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161 Selenium medicinal chemistry and cancer immunotherapy Tianfeng Chen

Department of Chemistry, Jinan University, Guangzhou 510632, China. Email: [email protected]

Chemical drug design based on the biochemical characteristics of cancer cells has become an importantstrategy for discovery of novel anticancer drugs to enhance the cancer targeting effects and biocompatibility, and decrease toxic side effects. Design of chemical molecules based on cancer cell signaling pathways has become an important strategy for discovery of targeting anticancer strategies. The applicant dedicates oneself to the design and synthesis of potential cancer-targeting drug delivery systems by chemical methods. We have synthesized various series of targeting selenium compounds and nanosystems, based on cancer molecular targets. Nonspecific absorption and clearance of nanomaterials during circulation is the major cause for treatment failure of nanomedicine-based cancer therapy. Therefore, herein bioinspired red blood cell membrane (RBC) is employed to camouﬂage 2D MoSe2 nanosheets with high photothermal conversion efficiency to achieve enhanced hemocompatibility and circulation time by preventing macrophage phagocytosis. RBC-MoSe2- potentiated photothermal therapy (PTT) demonstrates potent in vivo antitumor efficacy, which triggers the release of tumor-associated antigens to activate cytotoxic T lymphocyte and inactivate PD-1/PD- L1 pathway to avoid immunologic escape. Furthermore, in the ablated tumor microenvironment, the tumor associated macrophages are effectively reprogrammed to tumoricidal M1 phenotype to potentiate the antitumor action. The antitumor immune-regulation action and the effects on reprogramming of tumor-associated macrophages were also investigated. It is anticipated that the results from this project may provide a good strategy for rational design of the next-generation theranostic nanomedicines with specific drug targets and clear action mechanisms, and could provide a new breakthrough and new ideas for the multidisciplinary comprehensive treatment of tumors.

References [1] L. Chan, P. Gao, W. Zhou, C. Mei, Y. Huang, X.F. Yu, P.K. Chu, T. Chen, Sequentially Triggered Delivery System of Black Phosphorus Quantum Dots with Surface Charge-Switching Ability for Precise Tumor Radiosensitization, ACS Nano, 12 (2018) 12401-12415. [2] P. Feng, G. Ma, X. Chen, X. Wu, L. Lin, P. Liu, T. Chen, Electrooxidative and Regioselective C-H Azolation of Phenol and Aniline Derivatives, Angew Chem Int Ed Engl, 58 (2019) 8400-8404. [3] L. Zheng, C. Li, X. Huang, X. Lin, W. Lin, F. Yang, T. Chen, Thermosensitive hydrogels for sustained-release of sorafenib and selenium nanoparticles for localized synergistic chemoradiotherapy, Biomaterials, 216 (2019) 119220. [4] Lizhen He, Tianqi Nie, Xiaojun Xia, Ting Liu, Yanyu Huang, Xiaojuan Wang, Tianfeng Chen, Cancer Immunotherapy Designing Bioinspired 2D MoSe2 Nanosheet for Efficient Photothermal- Triggered Cancer Immunotherapy with Reprogramming Tumor-Associated Macrophages, Advanced Functional Materials, 29(2019) 1901240

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Vladimir Katanaev University of Geneva

Vladimir Katanaev is born in Siberia and is a graduate of Krasnoyarsk State University and Pushchino branch of Moscow State University, Russia. He received his PhD in 2000 from the Institute of Biochemistry, University of Fribourg. From 2000 to 2005 he worked as postdoctoral research fellow and subsequently as associate research scientist at the Department of Genetics and Development of Columbia University, New York. He then became Independent Group Leader at the University of Konstanz (Germany), where he also completed his Habilitation in 2010. He joined the Department of Pharmacology and Toxicology of the University of Lausanne (Switzerland) in April 2011 as Associate Professor, relocating his laboratory from Konstanz to Lausanne. He joined the Faculty of Medicine of the University of Geneva in October 2018, where he became a Full Professor and Chair at the Translational Research Center in Oncohaematology and at the Department of Cell Physiology and Metabolism. Biological nanostructures and nanocoatings and their translation into application through reverse engineering are among many directions of Prof. Katanaev’s research. In June 2019, Vladimir Katanaev was awarded the High-end Foreign Expert title of Fujian province at MinJiang University, China.

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163 Reverse engineering of natural self-assembled multifunctional nanocoatings

Mikhail Kryuchkov1, Huo Xu2, Oleksii Bilousov3, Jannis Lehmann4, Manfred Fiebig4, and Vladimir L. Katanaev1,2,5 1Department of Cell Physiology and Metabolism, Translational Research Centre in Oncohaematology, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland; 2Institute of Oceanography, MinJiang University, Fuzhou 350116, China. 3Department of Pharmacology and Toxicology, University of Lausanne, 1011 Lausanne, Switzerland; 4Department of Materials, ETH Zurich, 8093 Zürich, Switzerland; 5School of Biomedicine, Far Eastern Federal University, 690922 Vladivostok, Russian Federation; Email: [email protected]

Insect corneal surfaces harbor antireflective nanocoatings made of nipple-like protrusions or ridges of fused nipples. Their diversity is modeled with the Turing reaction-diffusion of two antagonistic chemical entities. Analysis in Drosophila and other insects highlights corneal cuticular protein(s) and wax lipid(s) as candidates for such entities. Using proteomics and genetics methods, we identify, in D.melanogaster and eleven other Drosophila species, both the protein component and the key enzymes in the corneal wax biosynthetic pathway, responsible for formation and diversity of corneal nanostructures. As genetic perturbations of the respective genes produce opposite effects on nanocoatings, they underlie the two antagonistic molecular entities cooperatively forming the nanopatterns. We establish low-cost recombinant production of the respective protein, which physically interacts with commercial wax lipids. In vitro admixtures of the protein and waxes coat artificial surfaces with stable nanostructures following the Turing principles. These studies identify the molecular mechanism of biological nanopatterning and are translatable into nanotechnological and nanomedical applications.

References: 1. Kryuchkov M, Blagodatski A, Cherepanov V, Katanaev* VL. Arthropod corneal nanocoatings: diversity, mechanisms, and functions. (2018) Book chapter to: Functional Surfaces in Biology III of the Springer Thematic Series Biologically Inspired Systems. Editors: Gorb E, Gorb S., ISBN 978-3- 319-74144-4. DOI: 10.1007/978-3-319-74144-42. 2. Kryuchkov M, Lehmann J, Schaab J, Cherepanov V, Blagodatski A, Fiebig M, Katanaev* VL. Alternative moth-eye nanostructures: antireflective properties and composition of dimpled corneal nanocoatings in silk-moth ancestors. (2017) Journal of Nanobiotechnology, 15:61. DOI: 10.1186/s12951-017-0297-y. 3. Sergeev A, Timchenko AA, Kryuchkov M, Blagodatski A, Enin GA, Katanaev* VL. Origin of order in bionanostructures. (2015) RSC Advances, 5: 63521-7. 4. Katanaev VL, Kryuchkov M. Insect corneal type nanocoatings. European patent application EP18175103.3, filed 30.08.2018.

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164

Xianghui Xu Nanjing Tech University College of Materials Science and Engineering

Dr. Xianghui Xu is a Professor in the college of Material Science and Engineering, Nanjing Tech University. He obtained his doctorate in Macromolecular Chemistry and Physics from Sichuan University and Bachelor in Biomaterials from Beijing University of Chemical Technology. His research focuses on the development of dendrimeric drugs and nanocarriers to address current dilemmas on disease diagnosis and treatment, through macromolecular and supramolecular design. He has published a series of research papers in top journals, such as Advanced Materials, Angewandte Chemie International Edition, ACS Nano, Advanced Functional Materials, Materials Horizons, Chemistry of Materials and Small.

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165 Bioinspired macromolecular and supramolecular construction of dendritic nanomimics defeats impermeable drug-resistant tumor Xianghui Xu,* Zhongwei Gu

College of Materials Science and Engineering, Nanjing Tech University, Nanjing, Jiangsu 210009, P.R. China Email: [email protected]

All around the world, clinical anticancer treatments are suffering from two formidable predicaments: multi-drug resistance and impermeable tumor tissue. However, first-line chemotherapy agents are difficult to penetrate into deep tumor tissue and arrive effective therapeutic concentration in each tumor cell, leading to fatal failure of antitumor treatment. In order to address these dilemmas, we proposed a bioinspired and smart design of dendrimeric nanomimics which not only can simulate the natural virus to overcome the multiple physiological/pathological barriers (especially impermeable tumor and multi-drug resistant cells), but also can remodel tumor microenvironment and cellular permeability. The dendrimeric nanomimics are expected to defeat impermeable drug-resistant cancer via bioinspired macromolecular and supramolecular strategy. Customized arginine-rich dendritic peptides are engineered to simulate viral protein transduction domains and globular protein architectures, and these dendritic peptides assemble into virus-like nanomimics in aqueous solution, organizing highly ordered secondary structure. The dendritic nanomimics hierarchically knocked down the multiple physiological barriers: (i) negatively-charged corona for optimal drug blood transportation; (ii) robust dendritic nanostructures to enhance passive tumor targeting; (iii) tumor-specific acidity conditions would activate the membrane-breaking ability for deep tissue penetration and high cell internalization, and (iv) stimuli-disintegration for site-specific sufficient intracellular drug delivery. On the other hand, these dendritic nanomimics are able to generate hyperthermia to remodel the permeability of tumor tissues and cell membranes. And in vitro and in vivo studies demonstrated that dendritic nanomimics could strongly assisted therapeutic molecules for high penetration into impermeable drug-resistant tumor. In vivo antitumor results suggested that dendritic nanomimics largely inhibited the growth of drug-resistant impermeable xenograft tumors and minimized the adverse effects of antitumor therapy. We have successfully developed dendritic nanomimics with tumor-adapting and tumor- remodeling ability to overcome impermeable multidrug-resistant cancer. The virus-like dendritic nanomimics could strongly break cell membrane and invade into tumor cells, and moreover, the robust nanomimics can penetrate from tumor vasculature into tumor tissue and each tumor cell. Meanwhile, dendritic nanomimics efficiently enhanced tumor penetration and cell internalization, through remodeling the permeability of tumor tissue and cells. We hope that this work will open up an innovative strategy of rational combination of tumor-adapting performances and tumor-remodeling functionality for combating theranostic dilemmas on multidrugresistant and impermeable cancers. Reference [1] Y. Li, X. Xu, X. Zhang, Y. Li, Z. Zhang, Z. Gu, Tumor-specific multiple stimuli-activated dendrimeric nanoassemblies with metabolic blockade surmount chemotherapy resistance, ACS Nano 11(1) (2017) 416-429. [2] Y. Li, X. Zhang, Z. Zhang, H. Wu, X. Xu, Z. Gu, Tumor-adapting and tumor-remodeling AuNR@ dendrimer-assembly nanohybrids overcome impermeable multidrug-resistant cancer, Materials Horizons 5(6) (2018) 1047-1057. [3] X. Zhang, X. Xu, Y. Li, C. Hu, Z. Zhang, Z. Gu, Virion-Like Membrane-Breaking Nanoparticles with Tumor-Activated Cell-and-Tissue Dual-Penetration Conquer Impermeable Cancer, Advanced Materials 30(27) (2018) 1707240.

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166

Xiangliang Yang Huanzhong University of Science and Technology Email：[email protected]

Prof. Yang is the vice president of Nanomedicine of Chinese Pharmaceutical Association, the vice president of Nanomedicine and Engineering of Chinese Society of Biomedical Engineering, the vice president of Nano-Oncology of Chinses Anti-Cancer Association. Prof. Yang is the Chief Scientist of the Major Research Program of “Nanomedicine for Liver Cancer” from the Ministry of Science and Technology of China. Also is the Panel Member of National Key Research and Development Plan "Nano Science & Technology" Key Project. In last 10 years, Professor Yang’s research insterests have focused on nanomedicine including nano drug delivery systems, nanodiagnostics and biomedical nanomaterials.

⚫ More than 300 papers have been published in international journals including Nature Biomedical Engineering, Nature Communications, Nano Letters, ACS Nano, Advanced Functional Materials, Biomaterials, Small, Journal of Controlled etc. with H-index 47. Selected as the Most Cited Chinese Researchers by Elsevier from 2014 to 2018. ⚫ More than 50 Chinese patents, 3 national new drug certificates and 15 national drug registration approvals have been awarded. ⚫ Three books on nanomedicine have been published as the editor-in-chief or the subeditor-in-chief. ⚫ Three Science and Technology Advancement Awards of Hubei Province (one time for 1st class, two times for 2nd class) have been honored.

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167 Advances in tumor targeting strategies of nanomedicine Xiangliang Yang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 Email: [email protected]

To ameliorate complex physiological barriers of tumor tissues, improve targeting delivery efficiency and PK/PD behavior of antitumor nanomedicine, we put forward “Five Features” strategies, which included long circulation, target accumulation, deep penetration, cellular Internalization, drug release. Based on “Five Features”, we developed targeting strategies in tumor therapy. First, non- PEGylation hydrophobicity reverse strategy. According to the unique microenvironment of tumor tissues, we developed temperature- and pH-responsive nanogels. These nanogels could realize hydrophobicity reverse, overcome PEG dilemma, enhance tumor targeting efficiency and tumor therapy effects finally. Second, biomechano-regulating strategy. We develop tumor cells-derived MPs drug delivery system. Through modulation in stiffness of MPs, the PK/PD behavior of MPs was enhanced significantly. Thirdly, hyperbaric oxygen plus (HBOplus) strategy. HBOplus was a common adjuvant therapy method in clinic. HBO could improve tumor hypoxia microenvironment, enhance accumulation and penetration of nanomedicine in tumor tissues. Meanwhile, HBO also make tumor cells sensitive against antitumor drug. Fourthly, HESylation strategy. In the basis of RES block, drug co-delivery and drug covalent coupling, we developed various HES drug delivery system, and realized enhanced tumor chemotherapy effects.

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168

Chong Li

Department of Bioengineering, University of Washington

Prof. Xiaohu Gao received his Ph.D. degree in bioanalytical chemistry from Indiana University, Bloomington, and his postdoctoral training from the Department of Biomedical Engineering at Georgia Tech and Emory University. He became a faculty member in the Department of Bioengineering at the University of Washington in 2005. He received the NSF CAREER Award in 2007, and has been a member of the American Chemical Society (ACS) and Biomedical Engineering Society (BMES) since 2003. He is also an elected fellow of AIMBE (the American Institute for Medical and Biological Engineering, class 2013). Dr. Gao’s research interest spans over biomedical nanotechnology, molecular engineering, molecular imaging, and therapeutics.

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169 Tagging biomacromolecules for intracellular imaging and therapy Xiaohu Gao

Department of Bioengineering, University of Washington, Seattle, WA, USA Email: [email protected]

Biomacromolecular agents such as DNA, RNA, proteins, and peptides are often superior in target binding specificity and easier to design compared to small-molecule imaging agents and drugs. A fundamental limitation for these large, highly water-soluble molecules, however, is their inability to access the intracellular space where the vast majority of biological activities take place. In this talk, I will discuss recent progresses we made on imaging and treating of intracellular targets. This project has the potential to greatly expand the target space for both diagnosis and therapy.

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170

Xiaoming He University of Maryland

He is a Professor of Bioengineering at the University of Maryland (UMD), College Park, MD. He received his B.S. and M.S. degrees in Thermal and Fluid Engineering from Xi’an Jiaotong University in 1995 and 1998, respectively. After teaching for two years in Beijing University of Technology, he went to the University of Minnesota-Twin Cities in 2000 for doctoral studies and obtained his Ph.D. degree in Mechanical Engineering in 2004. He then conducted postdoctoral training from 2004-2007 at Harvard Medical School and Massachusetts General Hospital. Afterward, he worked as an Assistant Professor at the University of South Carolina from 2007-2011, and Associate Professor and Full Professor at Ohio State University from 2011-2017. His current research is focused on developing micro and nanoscale biomaterials and devices to engineer totipotent, pluripotent, and multipotent stem cells for cancer theranostics and tissue regeneration including assisted reproduction. His research has been funded with him as the PI by various government agencies and private foundations including National Institutes of Health (NIH), National Science Foundation (NSF), and American Cancer Society. He has published more than 110 peer-reviewed articles in high-ranking journals such as Nature Nanotechnology, Nature Communications, Advanced Materials, ACS Nano, ACS Central Science, and Advanced Functional Materials, in addition to one book and four book chapters. He is serving as the Chair of the American Society of Mechanical Engineers (ASME) Biotransport Committee and an associate editor of Journal of Medical Devices. He is a fellow of the ASME and the American Institute of Medical and Biological Engineering (AIMBE)

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171 Cold responsive nanoparticle for overcoming cancer drug resistance Hai Wang and Xiaoming He

Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA Email: [email protected]

Although high temperature induced by laser, ultrasound, and electromagnetic field has been extensively studied to control nanoparticle-mediated delivery of therapeutic agents for the therapy or destruction of tumors for many years, cold temperature has not been explored in the field of drug delivery until recently. However, cold temperature has been widely utilized to treat various illnesses including cardiovascular diseases and cancer. We have developed novel cold-responsive nanoparticles that release their payload in response to cooling to below ~10 C. These nanoparticles encapsulated with anticancer drugs in combination with ice cooling can be used to overcome cancer multidrug resistance. This is attributed to the ice cooling triggered burst drug release from the nanoparticles and minimization of cell metabolism at cold temperature. The former surpasses the rate of drug efflux via the transmembrane efflux pumps overexpressed in multidrug resistant cancer cells, and the latter compromises the function of the efflux pump by minimizing the synthesis of ATP that drive the efflux pumps. Moreover, these nanoparticles are shown to preferentially accumulate in (i.e., target) tumor after intravenous injection. When combined with ice cooling, these nanoparticles efficiently inhibit the growth of multidrug resistant tumors in vivo without evident systemic toxicity. Collectively, our novel cold- responsive nanoparticles may find tremendous applications for addressing the challenge of cancer drug resistance.

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172

Xiaoxuan Liu

Institute of Pharmaceutical Sciences, China Pharmaceutical University

Dr. Xiaoxuan Liu is a Professor at the Institute of Pharmaceutical Sciences, China Pharmaceutical University (CPU). She received her Ph.D in 2010 from Wuhan University in China and Aix-Marseille University in France. After her Ph.D, she joined the Cancer Research Center of Marseille and Interdisciplinary Center on Nanoscience of Marseille in France and performed research for five years. During this period, she got two post-doctoral grants from l’Association pour la Recherche sur les Tumeurs de la Prostate (ARTP) and l’Association Française contre les Myopathies (AFM). On 2015, she was recruited as Specially-Appointed Professors by China Pharmaceutical University in China. On 2016, she was selected by the Thousand Youth Talents Plan. Her research interest is focus on developing multi-functional dendrimers as nanovectors for nucleic acid and drug delivery, which is interdisciplinary research program including chemistry, physics, biology and medicine. Originated from these research results, she has co-authored 28 publications. Some of them have been highlighted by Nature Chemistry and reported as frontispiece or cover story.

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173 Self-assembling amphiphilic dendrimers for on-demand delivery of siRNA therapeutics Dandan Zhu1, Ling Peng2, Xiaoxuan Liu*1 1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Advanced Pharmaceuticals and Biomaterials, China Pharmaceutical University (#24 Tongjiaxiang, Gulou District, Nanjing, 210009, China) 2 Aix-Marseille Université, CINaM, CNRS UMR 7325, Equipe Labellisé par La Ligue, Campus Scientifique de Luminy (163, avenue de Luminy, Marseille, 13288, France) Email: [email protected] RNA interference (RNAi) holds great promise for therapeutic applications. However, safe and successful clinical translation essentially requires further advancement of developing efficient delivery systems.[1] Among myriad nanocarriers, amphiphilic dendrimers, marrying the characteristic of dendrimers, self-assembly performance of amphiphilic molecules and the bio-mimicry of lipids, become particularly appealing as nano-vectors for drug delivery in nanomedicine, in particularly for small interfering RNA (siRNA) therapeutics. Here, we reported a series of amphiphilic dendrimers are able to self-assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the currently available non-viral vectors.[2,3] Furthermore, with the aim of developing nanocarriers to achieve on-demand delivery of siRNA therapeutics for the treatment of diseases such as cancers, we engineered our amphiphilic dendrimer based siRNA delivery systems with a dual targeting peptide bearing a RGDK warhead for targeted siRNA delivery [4] or specific reactive oxygen species (ROS) responsive moiety for ROS-responsive siRNA delivery for cancer treatment [5]. Our study demonstrates that the self-assembling amphiphilic dendrimers represent novel and versatile means for functional siRNA delivery, heralding a new age of dendrimer-based self-assembled drug delivery in biomedical applications.

References [1] M.P. Stewart, A. Sharei, X. Ding, G. Sahay, R. Langer, K.F. Jensen. In vitro and ex vivo strategies for intracellular delivery, Nature, 538(2016), 183-192. [2] T. Yu, X. Liu, A.L. Bolcato-Bellemin, et al. An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo, Angew. Chem. Int. Ed., 51(2012), 8478-8484. [3] X. Liu, J. Zhou, T. Yu, et al. Adaptive amphiphilic dendrimer-based nanoassemblies as robust and versatile siRNA delivery systems, Angew. Chem. Int. Ed. 53(2014), 11822-11827. [4] Y. Dong, T. Yu, L. Ding, et al A Dual Targeting Dendrimer-Mediated siRNA Delivery System for Effective Gene Silencing in Cancer Therapy, J. Am. Chem. Soc. 140(2018), 16264-16274. [5] X. Liu, Y. Wang, C. Chen, et al. A fluorinated bola-amphiphilic dendrimer for on-demand delivery of siRNA, via specific response to reactive oxygen species. Adv. Funct. Mater., 26 (2016), 8594-8603.

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174

Xiaoyang Xu New Jersey Institute of Technology Department of Chemical and Materials Engineering

Dr. Xiaoyang Xu is an assistant professor in the Department of Chemical and Materials Engineering at New Jersey Institute of Technology. Before that, he was a joint NIH postdoctoral fellow in the laboratories of Professors Robert Langer at MIT and Omid Farokhzad at Harvard Medical School. He completed his Ph.D. in Material Chemistry at Northwestern University under the supervision of Prof. Chad Mirkin. He received his B.E. in Chemical Engineering from East China University of Science and Technology in China. Dr. Xu’s research focus is the development of novel biomaterials and nanotechnologies for a variety of medical applications including diagnosis, bioimaging, drug delivery, and regenerative medicine. He is also interested in developing synthetic biomaterials and processing techniques to fabricate hydrogels and scaffolds for use in drug delivery and tissue engineering. Dr. Xu has over 15 years of experience in the synthesis, characterization and testing of a range of biomaterials and nanoparticles for medical applications, leading to over 40 peer-reviewed research articles and 10 issued/pending patents. His publications has been cited over 5,000 times. Dr. Xu has received multiple awards including Ruth L. Kirschstein National Research Service Award, AACR Scholar-in-Training Award, Chinese Government Award for Outstanding Chinese Students Study Abroad, and 1000 Plan Professorship for Young Talent.

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175

Nanoparticle mediated delivery of mTOR inhibitor for improved cancer pain management Xiaoyang Xu* Zhongyu Li

Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA Email: [email protected]

Cancer cell metastasis to bone subsequently induces bone pain and can be characterized as persistent and spontaneous pain as well as a “movement-evoked pain, which can severely compromise a patient’s quality of life. Morphine and other opioid analgesics are potent pain- relieving agents that are essential for pain management in cancer patients and neuropathic pain. Besides being the standard of care for the treatment of cancer-related pain in patients with advanced stage disease, opioids – especially morphine – are also routinely used for anaesthetic procedures in cancer patients undergoing surgery. However, most of neuropathic pain or cancer pain patients require high dose of opioids as well as repeated and prolonged administration of opioids to alleviate pain, continuous using opioids leads to many subsequent complications, such as tolerance, hyperalgesia, respiratory depression, and addiction, which strongly limits its clinical use. Therefore, it is important to decrease the risk of opioids such as morphine when using them for pain relief especially in cancer pain. Rapamycin is an immunomodulatory drug that targets the mammalian target of rapamycin pathway and can attenuate morphine-induced tolerance and hyperalgesia in rats with neuropathic pain. Other studies showed that rapamycin decreased or delayed the development of cancer-induced mechanical, heat, and cold hypersensitivity. Although prior studies considered that rapacymin can be a novel way for relief of cancer induced pain and morphine tolerance or hyperalgesia, clinical development of rapamycin has been impeded due to its poor solubility and the lack of efficient drug delivery carriers. Herein, we reported a protein nanoparticle-based rapamycin delivery system for opioid-induced tolerance and hyperalgesia management. We have demonstrated that our protein nanoparticle can efficiently encapsulate and deliver rapamycin. We observed that the intravenously administration of rapamycin nanoformulation can inhibit the protein expression of mTOR and its downstream factor S6k. We have also demonstrated that our rapamycin nanomedicine can reverse morphine induced analgesic tolerance and alleviate thermal hyperalgesia and mechanical allodynia after morphine withdrawal in morphine tolerance maintenance mice. This new mTOR inhibitor nano- delivery approach may open a new avenue by improving morphine analgesia and preventing the development of morphine analgesic tolerance and improve the life quality of patients suffering with cancer pain.

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176

Xiongbin Lu Indiana University School of Medicine

Dr. Xiongbin Lu is a Tenured Full Professor at the Department of Medical and Molecular Genetics, Indiana University School of Medicine. He is also Vera Bradley Foundation Endowed Chair in Breast Cancer Innovation and Strategic Research Initiative Distinguished Investigator at Melvin & Bren Simon Cancer Center. Dr. Lu obtained Bachelor from Zhejiang University and PhD in Biochemistry from Shanghai Institute of Biochemistry, Chinese Academy of Sciences. He then had his postdoctoral training at NIH and Baylor College of Medicine. He was awarded by American Cancer Society Research Scholar Grant and the Faculty Educator of MD Anderson Cancer Center. Dr. Lu is an elected Fellow of American Institute for Medical and Biological Engineering. His research interests include human cancer genomics, cancer biology, precision cancer therapy and immunotherapy. He has published over 100 papers in his research career, including a number of papers with him as corresponding author in high-impact journals such as Nature, Cancer Cell, Nature Nanotechnology, Molecular Cell, Journal of Clinical Investigation, EMBO Journal, and Nature Communications. He has also been actively collaborating with biomedical engineering scientists, which resulted in many high-quality papers published in Advanced Materials, ACS Nano, Biomaterials, and Nature Communications.

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177 Precision medicine for treating triple negative breast cancer with chromosome 17P loss Yunhua Liu1, Jiangsheng Xu2, Yujing Li1, Chi Zhang1, 3, Xiaoming He2, 4, 5, Xiongbin Lu1, 3, 6

1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA 2. Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA 3.Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA 4.Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, USA 5.Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, USA 6.Bren & Melvin Simon Cancer Center, and Vera Bradley Breast Cancer Center, Indiana University School of Medicine, Indianapolis, IN, USA Email: [email protected] (X.L.)

Triple-negative breast cancer (TNBC) is a clinically heterogeneous disease with diverse molecular features. The challenges for developing novel treatment approaches for TNBC are the paucity of actionable targets, lack of targeted therapies, and poor prognosis of patients. Breast cancer genomics revealed that heterozygous deletion of chromosome 17p (Chr17p) is one of the most prevalent events in human cancer, including TNBC (53%). Within the 17p deletion region is the tumor suppressor gene TP53 (encoding p53), whose mutation has been considered as a primary tumorigenic driver. However, it remains unclear whether the deletion event, which often includes as many as several hundred genes, impacts tumorigenesis beyond TP53 loss alone. Our bioinformatics analysis revealed that heterozygous deletion of Chr17p is tightly correlated with poor cytotoxicity of tumor infiltrating lymphocytes (TILs) and poor clinical outcomes in patients with TNBC, suggesting that selective advantage of Chr17p loss for tumor cells is the combined effect of the co-deleted genes in this region. Our recent study identified POLR2A in the TP53-neighboring region as a collateral vulnerability target in human cancer with Chr17p loss, suggesting that inhibition of POLR2A may be a precision therapy approach for the cancer with this genomic defect. We used α-amanitin, a natural small compound to specifically inhibit POLR2A. However, free form of α-amanitin causes liver toxicity, limiting its clinical applications. To overcome its toxicity, we have been developing α- amanitin-based antibody-drug conjugates (ADC). This type of ADC showed significant efficacy in inhibiting the growth of the tumors with heterozygous Chr17p loss as well as minimal toxicity in vivo. To develop a precision nanomedicine, we also designed a type of pH-activated nanoparticle (termed as nanobomb) for delivery of POLR2A small interfering RNA (siRNA), which enhances bioavailability and improves stability and endosomal release of the siRNA. We demonstrate that suppressing POLR2A expression with the siRNA-laden nanoparticles led to dramatic suppression of TNBC tumors with 17p loss. Collectively, we show that heterozygous deletion of Chr17p not only contributes to TNBC tumorigenesis, but also confers therapeutic vulnerabilities, which can be utilized to develop novel targeted cancer therapy.

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178

Xuehai Yan

Institute of Process Engineering, Chinese Academy of Sciences

Dr. Xuehai Yan obtained his PhD in chemistry at the Chinese Academy of Sciences (CAS) in 2008. After that, he moved to the Max Planck Institute of Colloids and Interfaces in Germany for postdoctoral research as an Alexander von Humboldt fellow. In 2013, he became a professor at the Institute of Process Engineering (IPE), CAS. He is the vice directors at the State Key Laboratory of Biochemical Engineering and the Center of Mesoscience, IPE, CAS. He is the editor of Colloids and Surfaces A. His research interests are mainly focused on peptide-modulated self-assembly, mesoscale mechanisms, supramolecular colloids and antitumor phototherapy. He has authored or co-authored more than 120 peer-reviewed articles, and is named in 15 patents or disclosures.

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179 Peptide-tuned self-assembly of phototheranostic supramolecular nanodrugs Xuehai Yan*, Ruirui Xing, Yamei Liu

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190 P. R. China Email: [email protected]

Proteins and peptides in biological systems can undergo self-assembly for formation of various high-level structures to achieve life functions and sustain life activities. Oligopeptides (peptides with low molecular weights) have the same primary structure as proteins, in which amino acids are the basic compositions. In comparison to proteins, oligopeptides have the advantages of molecular encoding sequence, flexible and controllable assembly, and have developed into an important building block. They may offer a new alternative for creating and developing new biomedical materials and technologies. In this presentation, oligopeptide will be employed for regulating self-assembly of photosensitizers for precise design of a variety of phototheranostic supramolecular nanodrugs. The key point of this suggested strategy is to rationally design and control the intermolecular interactions of peptides and photosensitizers, thus allowing for flexible modulation of both assembled structures and corresponding imaging and therapeutic functionalities. The assembled nanoparticles can show different theranostic properties depending on their dynamic structural evolution in vivo, especially in tumor of a mouse. Thus, the smart supramolecular nanodrugs can be well achieved and utilized for fluorescence imaging and photodynamic therapy or photoacoustic imaging and photothermal therapy against cancer. The structural dynamic evolution and corresponding therapeutic functions have been well demonstrated in living mice. Overall, this study offers alternative and potent ways for precise design of supramolecular nanodrugs based on small biomolecules combination and intermolecular interactions control.

References [1] R. Xing, Q. Zou, C. Yuan, L. Zhao, R. Chang, X. H. Yan, Self-assembling endogenous biliverdin as a versatile near-infrared photothermal nanoagent for cancer theranostics, Adv. Mater. 31 (2019) 1900822. [2] L. Zhao, Y. Liu, R. Chang, R. Xing, X. H. Yan, Supramolecular photothermal nanomaterials as an emerging paradigm towards precision cancer therapy, Adv. Funct. Mater. 29 (2019) 1806877. [3] S. K. Li, Q. L. Zou, Y. X. Li, C. Q. Yuan, R. R. Xing, X. H. Yan, Smart peptide-based supramolecular photodynamic metallo-nanodrugs designed by multicomponent coordination self- assembly, J. Am. Chem. Soc. 140 (2018) 10794–10802. [4] Q. L. Zou, M. Abbas, L. Y. Zhao, S. K. Li, G. Z. Shen, X. H. Yan, Biological photothermal nanodots based on self-assembly of peptide-porphyrin conjugates for antitumor therapy, J. Am. Chem. Soc. 139 (2017) 1921–1927. [5] K. Liu, R. R. Xing, Q. L. Zou, G. H. Ma, H. Möhwald, X. H. Yan, Simple peptide-tuned self- assembly of photosensitizers towards anticancer photodynamic therapy, Angew. Chem. Int. Ed. 55 (2016) 3036–3039.

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180

Xueqing Zhang Shanghai Jiao Tong University

Dr. Xueqing Zhang is an Associate Professor at the School of Pharmacy, Shanghai Jiao Tong University. She obtained her Ph.D. in Polymer Chemistry and Physics from Wuhan University, and completed her joint postdoctoral training at Massachusetts Institute of Technology and Harvard Medical School before she started her career with American companies as a Senior Engineer. She was a recipient of the prestigious Baxter Young Investigator Award, 1000 Young Talents Plan, and Innovative and Entrepreneurial talents in Jiangsu Province. Her research interests mainly focus on the development of novel biomaterials and nanotechnologies for a variety of medical applications including diagnosis, bioimaging, drug delivery, gene therapy and regenerative medicine. She has published 33 research articles in top journals including Science Translational Medicine, PNAS, Advanced Materials, Advanced Functional Materials, ACS Nano, Biomaterials, Small, among others. She has a h-index of 34 with total citation of more than 4000.

4th CASNN Annual Meeting 2019

181 Preparation of degradable and multifunctional gene delivery vectors via raft copolymerization [1] Qijing Chen, Xin Bai, Mingzhu Gao, Xueqing Zhang*

Engineering Research Center of Cell & Therapeutic Antibody Ministry of Education, School of Pharmacy Shanghai Jiao Tong University 800 Dongchuan Road, Shanghai 200240, P. R. China *E-mail: [email protected] Gene therapy is currently becoming an attracting strategy to treat cancers and genetic disorders. Development of safe and highly efficient gene delivery system is essential for the therapeutic application of gene therapy[1]. Non-viral cationic polymers have been widely investigated as effective gene vectors including polyethyleneimine (PEI), liposomes, poly(β-amino esters) (PBAEs). However, high toxicity of PEI and liposome, and poor solubility of PBAEs limit their clinical applications. It is urgent to seek for delivery alternatives with high gene delivery efficacy and low cytotoxicity both in vitro and in vivo. Glycidyl methacrylate (GMA) is commonly used to functionalize polymers due to its reactive epoxide group. Herein, GMA was chosen to react with various small molecules with only one primary amine and different tertiary amines to produce cationic structure including secondary and tertiary amines. However, PGMA-based polycations are not degradable due to their carbon-carbon backbones, which leads to their high toxicity. To solve this problem, we introduced degradability into the polymer backbone by copolymerizing GMA and a cyclic ketene acetal of 2-methylene-1,3-dioxepane (MDO). Reversible addition-fragmentation chain transfer (RAFT) polymerization, as one of the controlled radical polymerization methods, was chosen to synthesize well-defined polymers with low polydispersity and controlled polymerization degree. Moreover, the polymers prepared via RAFT method using the chain transfer agent (i.e. 4-cyano-4-[(ethylsulfanylthiocarbonyl)sulfanyl]pentanoic acid, CTA) have carboxyl and thiol terminal groups which could be functionalized with various fluorescent and targeting moieties (Fig. 1A). Three cell lines including HEK293, Hela and Raw264.7 were used to screen highly efficient and low toxicity gene transfection carriers. Well-defined PGMA polymers with degree of polymerization (DP) of 180 and 88 were synthesized, and 10 and 16 of ester units were respectively incorporated into the PGMA polymers namely P(GMA188-co-MDO10) and

P(GMA88-co-MDO16), as characterized by NMR and GPC. Three amines including APM, API and EA reacted with epoxides to produce corresponding polycations of PGAPM, PGAPI and PGEA (Fig. 1A). CCK8 assay and plasmid GFP reporter gene were used to assess the cytotoxicity and gene transfection efficiency. Polycations with DP of 88 showed better compatibility than those with DP of 180. Compared with PGAPM and PGAPI, PGEA showed the highest gene transfection efficiency in three cell lines. It is worth mentioning that P(GEA88-co-MDO16) showed significantly higher gene transfection efficiency than PEI at a polymer:DNA ratio of 90/1 (w/w) in HEK293 cells (Fig. 1B). Moreover, it also showed a high transfection efficiency with 14% GFP-positive cells in Raw264.7 cells belonging to the difficult-to-transfect category. After screened by cell viability and gene transfection assays, P(GEA88-co-MDO16) was a potential gene transfection carrier.

Fig. 1 Schematic diagram illustrating the preparation processes of RAFT prepared polycations (A) and fluorescence of HEK293 cells transfected with GFP gene using P(GEA88-co-MDO16) (B). Reference [1] H. Yin, K.J. Kauffman, D.G. Anderson, Delivery technologies for genome editing, Nat. Rev. Drug Discov., 16 (2017) 387-399.

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182

Xun Sun Sichuan University

Prof. Xun Sun is the Director & Professor of Department of Pharmaceutics, West China School of Pharmacy, Sichuan University. After postdoctoral training at University of Pennsylvania and University of Michigan, she joined the faculty of Sichuan University in 2008 and became a Professor in 2012. Prof. Sun’s current research centers on the delivery of biopharmaceuticals, especially for vaccines and nucleic acid based therapeutics. Prof. Sun has published more than 70 peer-reviewed papers as the corresponding author. She filed 12 patents and contributed chapters to 3 books. She is the Associate Editor of Journal of Controlled Release and the Deputy Editor of Molecular Therapy. She also serves as the editorial board member of and Acta Pharmaceutica Sinica B and the member of Chinese Pharmacopoeia Commission. Prof. Sun was the recipient of National Natural Science Funds for Excellent Young Scientist, the Royal Society Newton Advanced Fellowship (UK), the Nagai Foundation Tokyo International Scholarship, the Shulan Medical Prize, the first Prize of Sichuan Provincial Science and Technology Improvement Prize, Sichuan Youth Award for Science and Technology.

4th CASNN Annual Meeting 2019

183 Lymph node targeting for improved potency of cancer vaccine Hao Jiang, Xiaofang Zhong, Xiaoyu Hong and Xun Sun

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, China Email: [email protected]

Introduction: Numerous research has indicated that lymph nodes are not only reservoirs for immune cells and places for immune activation, but also are important targets for vaccines to enhance their potency [1]. Recently, lymph node targeting by passive drainage of nanoparticulate cancer vaccines to the lymph nodes has attracted increasing attention. This method makes use of the fact that nanoscale particles with a size between 10-100 nm can preferably drain to the lymphatics [2]. The easiness for surface modification and the ability of co-delivering antigen and adjuvant of nanoparticles offer additional options for optimizing cancer vaccine potency. Methods: We have developed various nano-sized delivery vesicles for cancer antigen and adjuvant, aiming for achieving efficient lymph node targeting and potent vaccine therapeutic efficacy. The delivery systems that were investigated include aluminum hydroxide polymer nanoparticles (APNs), aluminum-containing zeolitic imidazole nanoframeworks (ZANPs) and large pore mesoporous silica nanoparticles (MSNs). The fabricated particles were characterized in terms of size and surface properties and studied for their ability to target lymph node and induce anti-tumor immunity in murine models. Results: We successfully turned traditional aluminum hydroxide adjuvant from gel into nanoparticulate APNs with a size of about 90 nm and a slightly negatively charged surface. After subcutaneous injection, APNs quickly reached tumor draining lymph nodes within 6 h, where they were efficiently internalized by lymph node-resident antigen-presenting cells (APCs). The antigen and adjuvant loaded APNs significantly enhanced antigen specific immune responses, especially CD8+ T cell responses, finally leading to superior anti-tumor potency in both B16-OVA and B16F10 tumor- bearing mice. The fabricated OVA and adjuvant co-loaded ZANPs showed a size around 80 nm. At 10 h after subcutaneous injection, ZANPs had a 3.47-fold higher accumulation in tumor draining lymph node over that of free OVA. They elicited also significantly higher both cellular and humoral immunity than free antigen and adjuvant solution. Consequently, antigen and adjuvant loaded ZANPs effectively inhibited tumor growth and prolonged survival of mice in an EG7-OVA model. Most recently, we developed antigen loaded mesoporous silica nanoparticles (MSNs) with an overall size of about 80 nm and with different sized large pores. All the three types of MSNs showed significantly stronger migration ability to lymph node compared to free antigen solution, which were transformed to enhanced immune activation and tumor inhibition in a murine model. When comparing the MSNs with different pore sizes, MSNs with the largest pore size elicited the strongest immune responses and antitumor potency. Conclusion: These results indicated that by carefully designing nano-sized tumor antigen and adjuvant delivery systems, their lymph node targeting and antitumor efficacy can be significantly improved. This lymph node targeting strategy by passive drainage of nanoparticulate vaccines is promising for translation into clinical trials for cancer.

Reference: [1] H. Jiang, Q. Wang, X. Sun, Lymph node targeting strategies to improve vaccination efficacy, J. Control. Release, 267 (2017) 47-56. [2] N.L. Trevaskis, L.M. Kaminskas, C.J. Porter, From sewer to saviour-targeting the lymphatic system to promote drug exposure and activity, Nat. Rev. Drug Discov., 14 (2015) 781-803.

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184

Yaping Li

Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Professor Yaping Li is a principle investigator and director in centerof Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences. His research interests focus on the development and translation of biomaterials and technologies for targeted drug delivery. He has made a series of contributions to the basic research and clinic translation of targeted drug delivery systems, including the design, construction and mechanistic study of novel nanosized drug delivery systems with higher efficacy and less toxicity for the treatment of metastatic and multi-drug resistant cance

4th CASNN Annual Meeting 2019

185 Enhanced antitumor activity of ICB immunotherapy with in situ nanovaccines Bin Feng, Fangyuan Zhou, Dangge Wang, Tingting Wang, Haijun Yu, Yaping Li*

Center of Pharmaceutics & State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203 Email: [email protected]

Introduction: Immune checkpoint blockade (ICB) revolutionizes the field of cancer therapy, and kills cancer cells by unleashing suppressive barriers preventing the efficacy of antigen-specific cytotoxic T lymphocytes (CTLs). Despite the promising outcome in the clinic, the ICB is unable to induce new CTLs and its efficacy is limited by the density of tumor infiltrating lymphocytes (TILs). Moreover, ICB could also induce severe immune-related adverse effects (AEs) due to the off-tumor distribution of checkpoint blocking agents. So, drug delivery systems are urgently needed to realize the targeted delivery of drugs as well as prime anti-tumor immunity. Methods: To improve the efficacy of ICB, we designed a series of self-regulating nanomedicine that could trigger tumor-specific antigen release and presentation, and induce generation and infiltration of CTLs in response to the tumor microenvironment (TME). Tumor-specific delivery of checkpoint inhibitors has been achieved via the enhanced penetration and retention (EPR) effects, thus reducing the immune-related AEs induced by off-tumor drug distribution. Moreover, controllable drug release in response to acidic pH, TME-specific enzymes or near-infrared light further enhanced the therapeutic benefits and reduced AEs. Results: Fatty acid-modified prodrug of Oxaliplatin was first synthesized and self-assembled into TME-responsive liposome (MPV-HOAD). The MPV-HOAD was able to accumulate in the tumor through EPR effect, and improve drug delivery into the cancer cells through dePEGylation and charge reversal via MMP-2 and acid-enhanced cellular uptake. The combined chemotherapy and photodynamic therapy-induced immunogenic cell death (ICD) as confirmed by the release of calreticulin protein, adenosine triphosphate, and high-mobility group box 1 protein. The ICD improved CTL infiltration and facilitated the efficacy of anti-CD47-based ICB. The MPV-HOAD, inhibiting the growth, metastasis, and recurrence of the tumor [1]. Oxaliplatin-based prodrug also successfully encapsulated redox-responsive prodrug of NLG919, an inhibitor to IDO-1 enzyme. The binary nanoparticle induced ICD and CTL infiltration, and showed improved chemoimmunotherapy activity against metastatic breast cancer [2]. To further reduce the off-target adverse effects of ICB, we designed a hydrogel-based personalized vaccine for in situ delivery of PD-L1 inhibitor JQ-1 and photosensitizer ICG. The release of JQ-1 and ICG could be triggered under irradiation, realizing simultaneous ICD and ICB to inhibit the recurrence and metastasis of the tumor after resection [3]. Conclusion: These results demonstrated that TME-responsive and self-regulating nanomedicine could be used to induce antitumor immunity and potentiate ICB-based therapy.

References [1] F. Zhou, B. Feng, H. Yu*, D. Wang, T. Wang, Y. Ma, S. Wang, Y. Li*, Tumor microenvironment-activatable prodrug vesicles for nanoenabled cancer chemoimmunotherapy combining immunogenic cell death induction and CD47 blockade, Adv Mater. 31 (2019) 1805888. [2] B. Feng, F. Zhou, B. Hou, D. Wang, T. Wang, Y. Fu, Y. Ma, H. Yu*, Y. Li*, Binary cooperative prodrug nanoparticles improve immunotherapy by synergistically modulating immune tumor microenvironment, Adv Mater, 30 (2018) 1803001. [3] T. Wang, D. Wang, H. Yu*, B. Feng, F. Zhou, H. Zhang, L. Zhou, S. Jiao, Y. Li*, A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors, Nat Commun. 9 (2018) 1532.

4th CASNN Annual Meeting 2019

186

Yezi You University of Science and Technology of China

Dr Yezi You is now a professor of Department of Polymer Science and Engineering at the University of Science and Technology of China. He obtained his B. S. degree in 1996 form Hefei University of Technology, and M. S. degree in 2000 from University of Science and Technology of China, majoring in polymer chemistry. After obtaining his Ph.D. degree in 2003 at University of Science and Technology of China under the supervision of Prof. Cai-Yuan Pan, he spent a half year at Tokyo Institute of Technology as a visiting scholar, working with Prof. Tomiki Ikeda. Subsequently, he spent three years at Wayne State University as a postdoctoral fellow, working with Prof. David Oupicky. In 2007, He came back to University of Science and Technology of China as an associate professor. Since 2012, he has been a professor of Polymer Science and Engineering at the University of Science and Technology of China. He is the recipient of Education Ministry's New Century Excellent Talents Supporting Plan (2010), Distinguished Young Scholars Award (NSFC, 2016). He has published more than one hundred (100) peer-reviewed articles in Nat Commun, Adv Mater, Angew Chem, JACS, ACS Nano, Adv Func Mater, etc.

4th CASNN Annual Meeting 2019

187 High gene-transfection efficacy using phenylboronate micelles with highly selective membrane destruction Hai-Li Wang and Ye-Zi You *

Department, CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China (Hefei 230026, China) Email: [email protected]

Cationic polymers as vectors for gene delivery provide opportunities for improved safety, greater flexibility and more facile manufacturing [1]. However, their applications are bottlenecked by low transfection efficiency compared with viral vectors. Recently, great efforts have therefore been devoted to increasing the gene transfection efficiency of cationic vectors, however, due to that the cell uptake is it is low and it has some difficult to escape from endosome and enter nuclear, the transfection efficiency of cationic polymer is still much lower than that of viral vectors. Here, we reported the preparation of phenylboronate micelles, and the results have shown that they have highly selective ability of cell membrane-breaking: phenylboronate micelles can break cell membrane at pH below 6.5 while they can not break cell membrane at pH above 7.4. The self-assembly of polycationic polymers bearing a fluorocarbon core gave bioreducible cationic phenylboronate nanomicelles with phenylboronate units on the surface, which have a high DNA-binding affinity. The DNA- loaded polyplexes exhibited very high cellular-uptake efficiency and easy escape from endosome due to the ability endosomal membrane-breaking at endosomal acidic conditions. On the other, bioreducible cationic phenylboronate nanomicelles could also easily break nuclear membrane, which can help gene enter nuclear. The high DNA-binding affinity and the highly selective membrane-breaking of the formed micelles enabled the polyplexes to perform efficient gene transfection (~96% in 293T cells). What’s more, it is very interesting that the nanomaterials can punch many holes in the cells, leading to drug-deep penetration in multicellular tumor spheroids (MCTs). Therefore, the phenylboronate micelles with a highly selective membrane-breaking will be promising in gene delivery, transfection and effective gene therapy on cancer. A B 100 pH 5.0 pH 6.0 80 pH 7.4 60 40

20 RBC (%) hemolysis

0 B-PEA F6-B-F7 PEI

Figure 1. A) TEM images of red blood cell after treated with under pH of 6.0, B) hemolysis of red blood cell under various pH values. References [1] X. Liu, J. J. Xiang, D. C. Zhu, L. M. Jiang, Z. X. Zhou, J. B. Tang, X. R. Liu, Y. Z. Huang, Y. Q. Shen, Fusogenic reactive oxygen species triggered charge‐reversal vector for effective gene delivery, Adv. Mater. 28(2016), 1743-1752. [2] L. H. Wang, D. C. Wu, H. X. Xu, Y. Z. You, High DNA-binding affinity and gene-transfection efficacy of bioreducible cationic nanomicelles with a fluorinated core, Angew. Chem.Int. Edit. 55(2016), 755-759.

4th CASNN Annual Meeting 2019

188

Yi Hong University of Texas at Arlington

Dr. Yi Hong is an Associate Professor in the Bioengineering Department at the University of Texas at Arlington. He achieved his PhD in Material Science and Engineering in 2005 at Zhejiang University. And then Dr. Hong worked as a postdoc and later as a Research Assistant Professor in the McGowan Institute for Regenerative Medicine in the University of Pittsburgh from 2006 to 2012. After joined UTA in 2012, his research focuses on developing functional and bioactive soft biomaterials and translational research for tissue repair and regeneration, drug delivery and bio-imaging applications with emphasis on cardiovascular disease treatment and children/women health. He has published over 70 peer-review papers, applied/issued 11 patents, and over 100 conference abstracts. He received many honors and awards, such as AHA Beginning Grant-in-Aid award in 2014, NSF CAREER award in 2016, College of Engineering Outstanding Early Career Award (UTA) in 2018, and Junior Investigator Award from BMES ABioM-SIG (2018). He was elected as a Fellow of American Heart Association in 2017.

4th CASNN Annual Meeting 2019

189 Biodegradable nanoparticles enhancing bioadhesive strength Nikhil Pandey1, Luis Soto-Garcia1, Jun Liao1, Liping Tang1, Philippe Zimmern2, Kytai T. Nguyen1*, Yi Hong1* 1) Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019 2) Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390 Email: [email protected]

Introduction: Bioadhesives as tissue glues are highly attractive for wound healing because they can close wounds without sutures. However, the adhesive strengths of current clinical bioadhesives are weak with fast degradation [1]. Mussel-inspired bioadhesives are synthetic hydrogel systems using polymers grafted with catechol moieties, and they are promising as tissue glues because of their high adhesive strengths on wet interface [2], albeit these have lower adhesiveness than the mussel’s strong underwater adhesion. Inorganic silicate nanoparticles are capable of gluing a soft tissue such as a liver through strong interaction between nanoparticles and a tissue [3]. Thus, a combination of the mussel- inspired adhesive and biodegradable nanoparticles may offer synergistic effects on increasing the adhesive strength. Specifically, alginate or hyaluronic acid was chemically grafted with dopamine, and then blended with biodegradable poly(lactide-co-glycolide) (PLGA) based nanoparticles to form a nanocomposite adhesive. The tissue adhesive strengths were measured using an interface between porcine muscle and skin in vitro. Methods: A mussel-inspired polymer was synthesized by grafting dopamine onto oxidized alginate or sodium hyaluronate. Nanocomposites (NCs) were formulated by combining the mussel-inspired polymer with biodegradable nanoparticles, including PLGA nanoparticles (NPs), N- hydroxysuccinimide (NHS) modified PLGA NPs (PLGA-NHS) or polydopamine (polydopa) nanoparticles, using sodium metaperiodate (PI) as a crosslinker. These NCs were characterized for their tissue adhesive strengths (Uniaxial lap shear testing, cross head speed: 10mm min-1) on a porcine skin-muscle interface. The effects of nanoparticle concentration, nanoparticle type, and size on the tissue adhesion were investigated. The in vitro cytocompatibility of the optimized adhesives was evaluated using human dermal fibroblasts (HDFs), and in vivo tissue compatibility of the adhesives was assessed in a rat skin incision model. Results: The dopamine was covalently linked with the polymers. Mechanical testing of NCs on porcine skin-muscle interfaces revealed that blending nanoparticles with the adhesive hydrogels significantly enhanced the tissue adhesion strength. The lap shear strengths increased with the nanoparticle concentrations in the nanocomposites. The nanoparticle surface having NHS and catechol groups further enhanced the adhesive strength because the NHS and catechol surface could strengthen the interaction between the nanoparticles and tissues though covalent linkages. The in vitro HDF culture with the developed NC adhesives showed they had good cytocompatibility, and the in vivo skin incision also showed the NC adhesive had good tissue compatibility. Conclusions: The biodegradable nanoparticle addition significantly enhanced the adhesive strengths of the bioadhesives. The nanocomposite adhesives also showed great cell compatibility and tissue compatibility. These attractive properties imply that these nanocomposite adhesives have opportunities to be applied as tissue glues.

References: [1] Jeon O, Morezov JE, Alsberg E. Single and dual crosslinked oxidized methacrylated alginate/PEG hydrogels for bioadhesive applications. Acta Biomater 10 (2014):47-55 [2] Kord Forooshani P, Lee BP. Recent approaches in designing bioadhesive materials inspired by mussel adhesive protein. J. Polym. Sci. A Polym. Chem. 55(2017):9-33 [3] Rose S, Prevoteau A, Elzière P, Hourdet D, Marcellan A, Leibler L. Nanoparticle solutions as adhesives for gels and biological tissues. Nature 505(2014):382-385.

4th CASNN Annual Meeting 2019

190

Yiguang Wang Peking University

Prof. Yiguang Wang obtained his Ph.D. degree in Pharmaceutics from School of Pharmaceutical Sciences, Peking University in 2008. Then, he worked as a postdoctoral fellow in University of Texas Southwestern Medical Center for 5 years. During this period, he successfully developed an ultra-pH sensitive (UPS) nanoplatform based on the cooperative self-assembly of functional block copolymers for precise imaging and perturbation of endocytic organelles, broad tumor imaging with high contrast, and image- guided tumor surgery. Based on the UPS technology, a product (ONM-100) has been approved by FDA to start Phase II clinical trial in multiple cancer types in 2019. After the postdoctoral training in USA, he moved back to Peking University School of Pharmaceutical Sciences and worked as a principal investigator at State Key Laboratory of Natural and Biomimetic Drugs. Currently, Prof. Wang’s research group aims to design and develop smart nanomedicines to amplify biological signals (pH, enzyme, and hypoxia, etc.) or therapeutic efficacy to achieve precise tumor imaging and “on demand” drug delivery. In addition, he also focuses on the deep understanding of nano-bio interaction in vitro and in vivo by fluorescence imaging tools. Up to now, he has published 40 research papers, including Nature Materials, Nature BME, Nature Communications, Advanced Materials, JACS, Angew Chem Int Ed, etc, which have been cited more than 2000 times.

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191

Stimuli-responsive nanomedicine for precisely subcellular targeting and cancer theranostics Yiguang Wang

Stimuli-responsive nanomedicines have gained growing attention in a variety of biomedical applications such as molecular imaging, drug/gene delivery and immunotherapy. For cancer theranostics, smart nanomedicines have been fabricated for precise spatiotemporal control of drug delivery in response to exo/endogenous stimuli including pH, enzyme level, redox gradient, light, and temperature. Recently, we have engineered an ultra-pH-sensitive (UPS) nanotechnology based on the cooperative self-assembly of ionizable block copolymers to achieve specific targeting of catabolic organelles, precise amplification of tumor microenvironmental signals (e.g. pHe) for image-guided tumor resection. Moreover, the UPS nanotechnology has also been adopted for fluorescence-guided tumor surgery, photodynamic therapy, drug delivery and cancer immunotherapy. Based on the UPS technology, a product (ONM-100) has been approved by FDA to start Phase II clinical trial in multiple cancer types including breast cancer, head & neck carcinoma, colorectal cancer and esophageal cancer, etc.

4th CASNN Annual Meeting 2019

192

Ying liu

National Center for Nanoscience and Technology

2000 年 7 月毕业于天津医科大学医疗系，获得医学学士学位，专业为临床医学；2006 年 7 月

毕业于军事医学科学院基础医学研究所，获得博士学位，专业为生物化学与分子生物学；随后

在国家纳米科学中心从事博士后研究。2009 年留所至今，主要研究方向为纳米材料的生物学效

应与安全性。

迄今为止，申请人在生物材料、毒理学、纳米科学与药理学等领域的国际知名期刊 Acc Chem

Res，Nature Commun，PNAS，Nano Lett，ACS nano 等共发表 SCI 论文 64 篇，全部论文 SCI

他引 3500 余次，其中 11 篇论文入选 ISI web of knowledge-ESI 统计的“近十年高引频论文”。

2016 年获得国家“优秀青年”科学基金资助，2018 年获“中国毒理学会优秀青年科技奖”，

“中国科学院青年创新促进会”优秀会员；2018 年国家自然科学二等奖（第 2 完成人），“中国

科学院卢嘉锡青年人才奖”。“中国毒理学会青年委员会”委员，“中国毒理学会纳米毒理学专

业委员会”委员。国家重点研发计划“食品安全关键技术研发”重点专项课题负责人，国家自

然科学基金优秀青年和面上项目负责人；作为骨干参与科技部 973 项目、中科院知识创新工程

项目、丹麦国际合作项目等。

1995.9-2000.7 for Bachelor Degree in Tianjin Medical University; 2000.9-2003.7 for M.E. in Hebei Medical University; 2003.9-2006.7 for Ph.D in Academy of Military Medical Sciences; 2006.8-Present Post-doctor/Assistant professor/Associate professor in National Center for Nanoscience and Technology (NCNST) of China Research Directions: (1) Nanomedicine: Therapy for malignant tumor using nanoparticles. (2) Nanoparticles used for tissue Engineering

4th CASNN Annual Meeting 2019

193 Biological effects of environmental nanoparticles

Dongqi Ni, Jie Ding, Chunying Chen, Ying Liu CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China Email: [email protected]

Lung cancer is the most commonly diagnosed cancer and remains the leading cause of cancer death, with very low survival rates associated with metastasis. The positive relationship between particulate matter (PM) and lung cancer has been confirmed through epidemiological studies. Early metastasis is initiated by epithelial-mesenchymal transition (EMT) of lung cells, consisting of molecular rearrangements and cell changes from inactive epithelial cells into active mesenchymal cells that can metastasize. Long-term exposure to particulate matter (PM) of different diameters was demonstrated to significantly increase the EMT process of lung cancer cells, thereby promoting tumor metastasis to the liver in vivo. Lung cancer cells exposed to PMs showed decreased expression of the epithelial cell markers, E-cadherin and γ-catenin and an increase in expression of the mesenchymal cell markers, Vimentin and Fibronectin-1, indicative of the induction of EMT. The effects of PMs with a diameter of < 0.49 μm were significantly greater compared to exposure to the larger sized PMs. These data suggest that smaller PMs may be able to more easily penetrate cells, followed by increased ability to damage cells. Moreover, the levels of gaseous co-pollutants as well as PM might increase significantly. The expression patterns of microRNAs may serve as valuable signatures of exposure to environmental constituents. We exposed macrophages to the whole stream of outdoor air at the air-liquid interface aiming at closely approximating the physiological conditions and the inhalation situation in the lung. 58 miRNAs were up-regulated, and 68 miRNAs were down-regulated compared to filtered-air exposed control cells. The target genes of the up-regulated miRNAs were enriched in immunity- and inflammation-linked pathways, such as the TLR-NF-κB pathway. Compared to the group with higher concentrations of particles, 29 miRNAs were up-regulated, and 23 miRNAs were down-regulated in the cells exposed to air with higher concentrations of particles, SO2 and nitrogen oxide. The target genes of the up-regulated miRNAs were mostly enriched in apoptosis, adhesion and junction-related pathways. These results preliminarily unravel part of the toxic mechanisms of air constituents and provide clues for discovering the main drivers of air pollution-induced disorders.

4th CASNN Annual Meeting 2019

194

Yong Wang Penn State

Prof. Wang is Professor of Biomedical Engineering at Penn State. He received his B.S. degree (1995) in Environmental Chemistry from Jilin University and M.S. degree (1998) in Chemical Engineering from the Chinese Academy of Sciences, respectively. He got his PhD degree from Duke University and accomplished his postdoctoral training at Duke University Medical Center. He started his tenure- track assistant professor position in 2006. He was early promoted to Associate Professor in 2011 and Full Professor in 2016. His research is focused on programmable biomaterials for drug delivery, regenerative medicine and clinical diagnosis. His research findings have been published in journals such as Nat. Biotechnol., Nat. Comm.，Angew. Chem. Int. Ed., J. Am. Chem. Soc., Biomaterials, etc.

4th CASNN Annual Meeting 2019

195 In situ manufacturing of functional nanomaterials on the surface of live cells Yong Wang

Department of Biomedical Engineering, Penn State, University Park, PA 16802.

Live cells have been widely studied for biomedical applications such as cancer immunotherapy, drug delivery, tissue engineering, molecular sensing, etc. As cells are used as either a carrier or a functional component, the ability to engineer their surface may find new functions for better outcomes in those applications. Thus, effort has been made to engineer the surface of live cells. However, currently available nanotechnology strategies were primarily developed based on the concept of targeted nanoparticle delivery, i.e., relying on the use of pre-formed nanomaterials and the recognition of the nanomaterials and the cell surface. It inevitably causes various issues such as cytotoxicity, nanoparticle uptake, and/or insufficient surface coverage. In this talk, I will discuss a new concept for the nano-functionalization of the cell surface. In this concept, a supramolecular DNA nanomaterial will be in situ grown on live cells. As DNA molecules can hybridize with their complementary sequences, the supramolecular DNA nanomaterial has the capability of further hybridizing with any molecules or nanoparticles modified with their complementary sequences. Thus, the live cells can be functionalized at the nanoscale without theoretical limits. To demonstrate potential applications, I will discuss how to apply the engineered cells for tissue engineering and stem cell delivery.

4th CASNN Annual Meeting 2019

196

Yongming Chen

Sun Yat-sen University

Yongming Chen received his Master degree in 1990 from Northwest University. In 1993, he obtained his Ph.D. from Nankai University. From 1994 to 1998, he was Postdoctoral Researcher and later Research Assistant at the Institute of Chemistry, CAS. Then he spent the period 1998−2001 as Postdoctoral Researcher in University of Düsseldorf and University of Mainz. Since 2001, Chen was Professor at the Institute of Chemistry CAS. He moved to Sun Yat-sen University in 2013. Professor Chen’s research interests are in the areas of synthesis of well-defined polymers and polymer application in nanomedicine. He obtained “Distinguished Young Scholars” by National Science Foundation of China (2006) and “Wang Bo-Ren Polymer Research Award” by Chinese Chemistry Society (2011).

4th CASNN Annual Meeting 2019

197 Molecular bottlebrush as a unimolecular vehicle for nanomedicine Yongming Chen*, Huaan Li, Ziyong Sun

School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, China

Size and shape of delivery system are two basic structural factors mattering the fate of delivered substances. While the size has been extensively studied, the shape is far from known. Polymeric nanoparticles by molecular self-assembly have been widely used as drug delivery systems. However, two issues are critical. One is de-assembled concern. Due to the entropic self-assembled process, these nanocarriers may de-assemble in the circulating environment before reaching target. Another one is the shape control. Although, block copolymers may form cylindrical micelles, it is hard to prepare in the delivery system and to control the length. Different from the block copolymer self-assemblies, molecular bottlebrush (MBB) has a precisely controlled chemical structure and tunable shape, and, moreover, exhibits instinct stability. We are applying MBB as nanovehicle to explore the properties to challenge the problems of nanomedicine. Herein, a kind of MBB unimolecular micelle was constructed as unimolecular nanovehicle for photothermal cancer therapy. The MBB with pendent hydrophobic units provided a space for encapsulating IR780. Also, the MBB had polyacrylic acid segments with negative charge that interacts with cationic IR780. A polyethylene glycol shell offers MBB water solubility and protein resistance. It is highlighted that the MBB molecules allowed efficient drug loading with the content of up to ca. 25% and maintained their molecular morphology in cell culture medium. Among sphere, rod and worm, the rodlike MBB showed best 2D cellular uptake, 3D cell spheroids penetration, and preferential tumor accumulation in vivo as well. In addition, rodlike MBB effectively controlled tumor growth and thus demonstrated unique application. Also, we will show MBB to deliver agonists for targeting draining lymph nodes in nanovaccine development.

A B B57-IR780 B122-IR780 B747-IR780

30 nm PEG PHEMA PAA IR780

200 nm

C D E x v iv o 3 .0 1 4 0 0 0 IR 7 8 0

1 2 0 0 0 B 5 7 -IR 7 8 0 2 .5 y

y B 1 2 2 -IR 7 8 0 t t i 1 0 0 0 0 i s

s 2 .0 n B 7 4 7 -IR 7 8 0 n

e 8 0 0 0 t e t n I

n 1 .5

I 6 0 0 0

n n a a 1 .0 e 4 0 0 0 e M M 0 .5 2 0 0 0 0 B57-IR780 B122-IR780 B747-IR780 0 .0 t r g s r n r e n o i a e n y a B 5 7 - IR 7 8 0 B 1 2 2 - IR 7 8 0 B 7 4 7 -IR 7 8 0 e iv e u e m r L l L n u H p d B S i T K

Figure Structure and morphology of IR780-loaded MBB unimolecular nanoparticles.

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Yongzhuo Huang

Shanghai Institute of Materia Medica

Chinese Academy of Sciences

Professor Yongzhuo Huang obtained his Ph.D. from Zhejiang University (China), and conducted his postdoctoral training at the University of Michigan, Ann Arbor (USA). Prof. Huang has been endorsed by the prestigious Excellent Young Investigator program of National Natural Science Foundation of China, and the Hundred-talent Scholar Program of Chinese Academy of Sciences. His research focus is cancer nanotechnology-based therapeutic strategies and drug delivery.

4th CASNN Annual Meeting 2019

199 Targeting tumor-associated macrophage and metabolism as "two-birds- one-stone" therapeutic strategy Yongzhuo Huang

The tumor microenvironments (TME) represent a complicated network of various tumor composites that suppress the therapeutic responses and lead to drug resistance. The regulation of the immune subsets of TME could be helpful to remodel the TME and achieve functional normalization. For instance, tumor-associated macrophages (TAM) are abundant, representing the major population of innate immune cells at the TME and accounting for a portion even up to 50% in the tumor mass. The repolarization of TAM from the protumor M2 subtype toward antitumor M1 can serve as a potent target for cancer therapy. Meanwhile, glucose metabolism in tumor and its metabolite also play an important role in cancer development and growth. Therefore, targeting TAM and glucose metabolism is a promising avenue for remodelling the TME and inhibiting tumor growth.

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200

Yuan Ping Zhejiang University

Dr. Yuan Ping is currently a Professor at College of Pharmaceutical Sciences, Zhejiang University. He obtained Bachelor degree in Pharmacy and Master degree in Pharmaceutics, respectively, and obtained his PhD degree in Biomaterials from National University of Singapore in 2012. He pursued his postdoctoral training at Singapore Institute of Materials Research and Engineering, The University of Melbourne, and Nanyang Technological University for drug delivery research from 2012-2017. Dr. Ping’s current research mainly focuses on protein drug delivery and delivery of genome editing tools, and his multidisciplinary research has produced more than 30 original research papers in the fields of drug delivery, nanomedicine, biomaterials etc. in the past ten years. Dr. Ping was the recipient of German Academic Exchange Service (DAAD) research visit award, and the fellow of National ‘Thousands Talent Plan’ (Young Professional Program).

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201 Delivery of therapeutic genome-editing agents

Yuan Ping College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

The clustered, regularly interspaced, short palindromic repeat (CRISPR)-associated nuclease 9 (CRISPR/Cas9) is emerging as a promising genome editing tool to treat diseases in a precise way, and now it has been applicable to a wide range of research in the areas of biology, genetics, and medicine. Delivery of therapeutic genome-editing agents provides a promising platform for the treatment of genetic disorders. Although viral vectors are widely used to deliver CRISPR/Cas9 elements with high efficiency, they suffer from several drawbacks such as mutagenesis, immunogenicity, and off-target effect. Recently, non-viral vectors are emerging as another class of delivery carriers in terms of their safety, simplicity, and flexibility. In this talk, I will discuss the modes of CRISPR/Cas9 delivery, the barriers in the deliver process and the application of CRISPR/Cas9 system for the treatment of genetic disorders. I also highlight several representative types of non-viral vectors, including the one we have developed for the therapeutic delivery of CRISPR/Cas9 system in our lab. The applications of CRISPR/Cas9 in treating genetic disorders mediated by the non-viral vectors are also discussed.

References [1] T. Wan, D. Niu, C. Wu, F-J Xu, G. Church, Y. Ping, Material solutions for delivery of CRISPR/Cas-based genome editing tools: current status and future outlook. Mater. Today 26 (2019) 40-66. [2] C. Liu, T. Wan, H. Wang, S. Zhang, Y. Ping, Y. Cheng, A boronic acid-rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR/Cas9 gene editing. Sci. Adv. 5 (2019) eaaw8922.

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202

Yucai Wang School of Life Sciences, University of Science and Technology of China

Dr. Wang received his B.S. and doctoral degrees in polymer chemistry from the University of Science and Technology of China (USTC) in 2005 and 2010, respectively. He worked as a postdoctoral fellow at the Georgia Institute of Technology and University of Chicago from 2011 to 2015. In 2015, Dr Wang joined USTC as a professor at the School of Life Sciences supported by the “Young Thousand Talents Plan”. His current research focuses on the applications of nanomedicines to re-programme the tumor microenvironment to enhance anticancer therapy efficacy, and revealing the biointerfaces of nanomedicines. He has published more than 80 scientific papers high-impact journals like Nat Mater, Nat Commun, PNAS, Nano Letters, and ACS Nano with total citations of over 4000 and a h-index of over 40.

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203

“EPR EFFECT” of polymer nanomedicines in metastatic cancers Zhao Yangyang, Wang Qin, Dou Jiaxiang, Wang Yucai*

School of Life Sciences, University of Science and Technology of China, Hefei, 200027, China Email: [email protected]

Polymeric nanocarriers can efficiently deliver cargos to primary tumor via enhanced permeability and retention (EPR) effect, which substantially improves the drug concentration inside the tumors. Malignant tumors metastasize during progression, leading to the failure of tumor treatment.1 Due to its rich blood supply, liver is the main site of metastasis for many cancers, such as gastrointestinal and extragastrointestinal.2 Developing strategies for treating liver metastasis is of great significance in clinics. In this work, we studied the biological interface of polymeric nanomedicines and liver metastatic nodules of colorectal cancers. We aimed to address the concern that whether EPR effect exists in metastatic cancers. Our findings include that the nanomedicines accumulated efficiently in liver metastases by two ways. First, they can leak from hepatic sinusoids that were destroyed by the metastatic cancer cells and then penetrate into the interior of unvascularized metastases (diameter< ~100 μm). Second, the nanomedicines accumulate efficiently in vascularized metastases (diameter> ~100 μm) via the disrupted hepatic sinusoids and neovasculars. Our work will open up a path to the treatment of metastatic cancers using nanomedicines.

Figure 1. (A) Metastatic cancers destroyed peripheral hepatic sinusoids. (B) The accumulation mechanism of nanomedicines in metastatic nodules, which is independent of the well-known EPR effect.

References [1] P. Steeg, Targeting metastasis, Nat. Rev. Cancer 16 (2016) 201-218. [2] G. Van den Eynden, A. Majeed, M. Illemann, P. Vermeulen, N. Bird, G. Høyer-Hansen, P. Brodt, The multifaceted role of the microenvironment in liver metastasis: biology and clinical implications. Cancer Res. 73(2013) 2031-2043.

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204

Yunbing Wang

Sichuan University

Dr. Yunbing Wang is the Director of Chinese National Engineering Research Center for Biomaterials, Vice President of Chinese Society for Biomaterials, and Director of Engineering Research Center in Biomaterials of Sichuan University.

Dr. Wang’s current research interest is in the area of advanced biomaterials and implantable medical device development for the treatment of cardiovascular disease, diabetes, cancer and eye disease, etc.

Before taking his current position, he worked at different medical device companies including Medtronic, Boston Scientific, Abbott and CooperVision, and worked as the technical leader and leading inventor of several world-first products development, including bioresorbable stent for cardiovascular disease treatment and artificial pancreas device system for diabetes treatment. Prof. Wang is an inventor of more than 100 issued US patents, an author of around 100 published scientific papers.

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206

Prof. Zhaohui Tang

Changchun Institute of Applied Chemistry, Chinese Academy of Sciences

Dr. Zhaohui Tang is an Professor at the Changchun Institute of Applied Chemistry (CIAC), Chinese Academy of Sciences. He obtained his PhD in Polymer Chemistry from CIAC and was trained in the department of Chemistry at the Imperial College London and the State University of New York at Stony Brook as a postdoc fellow. He was elected into the Outstanding Member of Youth Innovation Promotion Association of the Chinese Academy of Sciences in 2015. His research interests focus on Nanomedicine for tumor treatment. He has published over 100 publications over his scientific career, in top journals like Advanced Materials, Progress in Polymer Science, Advanced Science, Chemical Science, Small and Biomaterials. He has a h-index of 39 with total citations of more than 4300.

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Polymeric conjugation improves the tumor vessel targeting of vascular disrupting agents Zhaohui Tang*, Wantong Song, Haiyang Yu, Xuesi Chen

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China Email: [email protected]

Tumor blood vessels are attractive target for solid tumor treatment. It has been reported that when solid tumors grow to a size larger than 2-3 mm3, the continued growth of tumors strongly depends on angiogenesis. As a result, various drugs inhibiting the growth of new blood vessels (angiogenesis inhibitors) or damaging the vasculature of cancer tumors (vascular disrupting agents, VDAs) have been developed. Combretastatin A4 phosphate (CA4P) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) are leading VDAs, however, they showed only moderate anti-tumor effects in clinical trials. A key reason for this is the low targeting of CA4P and DMXAA to tumor blood vessels as well as their rapid clearance from blood circulation system and tumor tissues. Recently, we have proposed poly(amino acid)-VDA conjugates to fully liberate the potential of VDAs on tumor therapy [1,2]. Enhanced accumulation and retention of VDAs in tumor tissue, especially, high distribution and gradual release around tumor blood vessels for poly(amino acid)-VDA conjugates resulted in prolonged vascular disruption and markedly enhanced therapeutic efficiency. We examined and compared the therapeutic effect of poly(amino acid)-VDA conjugates and small molecular CA4P/DMXAA in vivo. The poly(amino acid)-VDA conjugates showed significantly prolonged retention in plasma and tumor tissue. Most importantly, the VDA conjugates were mainly distributed around the tumor vessels because of their low tissue penetration in solid tumor. Pathology tests showed that the poly(amino acid)-VDA conjugates treatment led to continuous vascular occlusion and tumor damage after a single injection, this in contrast to small molecular vascular disrupting agent treatment, which showed quick relapse at an equal dose. Poly(L-glutamic acid)-combretastatin A4 conjugate treatment led to a tumor suppression rate (TSR) of 74%, indicating a significant advantage when compared to the TSR (24%) of CA4P group. Thus, the polymeric conjugation provide a new idea for enhancing the tumor-blood vessels-targeting and therapeutic effect of VDAs in solid tumor treatment.

References [1] S. Lv, Z. Tang, W. Song, D. Zhang, M. Li, H. Liu, J. Cheng, W. Zhong, X. Chen, Inhibiting Solid Tumor Growth In Vivo by Non-Tumor-Penetrating Nanomedicine, Small, 13 (2017) 1600954. [2] T. Liu, D. Zhang, W. Song, Z. Tang, J. Zhu, Z. Ma, X. Wang, X. Chen, T. Tong, A poly(l- glutamic acid)-combretastatin A4 conjugate for solid tumor therapy: Markedly improved therapeutic efficiency through its low tissue penetration in solid tumor, Acta Biomater., 53 (2017) 179-189.

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208

Zhen Gu Department of Bioengineering, University of California, Los Angeles (UCLA)

Dr. Zhen Gu is a Professor in the Department of Bioengineering and Director of the NIH Biotechnology Training in Biomedical Sciences and Engineering Program at the University of California, Los Angeles (UCLA). Dr. Gu received his B.S. degree in Chemistry and M.S. degree in Polymer Chemistry and Physics from Nanjing University. In 2010, he obtained Ph.D. at UCLA, under the guidance of Dr. Yi Tang in the Department of Chemical and Biomolecular Engineering. He was a Postdoctoral Associate working with Dr. Robert Langer at MIT and Harvard Medical School during 2010 to 2012. Before he moved to UCLA in 2018, he had been appointed as a Jackson Family Distinguished Professor in the Joint Department of Biomedical Engineering at the University of North Carolina at Chapel Hill and North Carolina State University. Dr. Gu’s group studies controlled drug delivery, bio-inspired materials and nanobiotechnology, especially for cancer and diabetes treatment. He has published over 170 research papers and applied over 70 patents. He serves as an Associate Editor for Nano Research and Science Advances. He is also an Inaugural Chair of the Bioinspired and Biomimetic Delivery (BBD) Focus Group in the Controlled Release Society (CRS). Dr. Gu is the recipient of the Sloan Research Fellowship (2016), Small Young Innovator Award (2019), Biomaterials Science Lectureship Award (2018), Young Investigator Award of CRS (2017), Alcoa Foundation Research Achievement Award (2017), Pathway Award of the American Diabetes Association (ADA, 2015) and Young Innovator Award in Cellular and Molecular Engineering of the Biomedical Engineering Society (BMES, 2015). MIT Technology Review listed him in 2015 as one of the global top innovators under the age of 35 (TR35). He was elected to the College of Fellows of the American Institute for Medical and Biological Engineering (AIMBE) in 2019.

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209 Glucose-responsive insulin and delivery devices Zhen Gu

Department of Bioengineering, University of California, Los Angeles (UCLA), Los Angeles, California 90095, United States Email: [email protected]

Closed-loop drug delivery systems have proven to be a practical strategy for homeostatic regulation, by tuning drug release as a function of biosignals associated with physiological and pathological processes. Among them, a glucose-responsive “closed-loop” insulin delivery system mimicking the function of pancreatic cells holds great promise to improve quality of life and enhance health in people with type 1 and advanced type 2 diabetes [1]. In this talk, I will introduce our ongoing efforts in developing glucose-responsive insulin and related delivery formulations and devices [2,3]. I will first discuss the transdermal microneedle patches integrated with glucose-sensitive components for self-regulated insulin delivery tested on both mice and pigs [4]. I will further introduce synthetic beta cells with vesicle fusion-mediated mechanism for glucose-responsive insulin “secretion” [5]. In addition, I will present our latest study of conjugating glucose transporter inhibitor to insulin for mitigating hypoglycaemia [6].

References [1] J. Wang, Z. Wang, J. Yu, A.R. Kahkoska, J.B. Buse, Z. Gu, Glucose-responsive insulin and delivery systems: innovation and translation, Adv. Mater. (2019) in press. [2] N. Bakh, M. Cortinas, M. Weiss, R. Langer, D. Anderson, Z. Gu, S. Dutta, M. Strano, Glucose- responsive insulin by molecular and physical design, Nat. Chem. 9 (2017) 937-943. [3] J. Wang, J. Yu, Y. Zhang, X. Zhang, A.R. Kahkoska, G. Chen, Z. Wang, W. Sun, L. Cai, Z. Chen, C. Qian, A. Khademhosseini, Q. Shen, J.B. Buse, Z. Gu, Charge-switchable polymeric complex for glucose-responsive insulin delivery, Sci. Adv. (2019) in press. [4] J. Yu, Y. Zhang, Y. Ye, R. DiSanto, W. Sun, D. Ranson, F.S. Ligler, J.B. Buse, Z. Gu, Microneedle- array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery, Proc. Natl. Acad. Sci. U. S. A. 112 (2015) 8260-8265. [5] Z. Chen, J. Wang, W. Sun, E. Archibong, A.R. Kahkoska, X. Zhang, Y. Lu, F.S. Ligler, J.B. Buse, Z. Gu, Synthetic β-cells for fusion-mediated dynamic insulin secretion, Nat. Chem. Biol. 14 (2018) 89-93. [6] J. Wang, J. Yu, Y. Zhang, A.R. Kahkoska, Z. Wang, J. Fang, J.P. Whitelegge, S. Li, J.B. Buse, Z. Gu, Glucose transporter inhibitor-conjugated insulin mitigates hypoglycemia, Proc. Natl. Acad. Sci. U. S. A. 116 (2019) 10744-10748.

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210

Zhengwei Mao Zhejiang University

He received a Ph.D. at Zhejiang University in the field of Materials Science and had a postdoc experience at Max Planck Institute of Colloids and interfaces, Germany. Dr. Mao’s research is focused on polymeric biomaterials, and seeks to control microstructure of materials for the purpose to manipulating the responses of cells and tissues, with the application for cancer therapy and tissue regeneration. Dr. Mao has published more than 100 papers in scientific journals including Nat. Comm., J. Am. Chem. Soc., Biomaterials, and so on. His research has received international attention and “young investigator award” from Chinese Association of Biomaterials. He now serves as one of the two editors of Materialia.

4th CASNN Annual Meeting 2019

211 Supramolecular interaction based polymeric nanomedicine for multimodal cancer therapy

Zhengwei Mao

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. E-mail: [email protected]

The development of smart drug delivery systems with favourable biocompatibility, high drug loading capacity, excellent circulation stability in vivo, potent anti-tumour activity, and multimodal imaging functionalities are of importance for future clinical application. The premature burst release and poor degradation kinetics indicative of polymer-based nanomedicines remain the major obstacles for clinical translation. Supramolecular interactions provide various structure flexibility and dynamic nature for programmed drug delivery. Herein we take the advantage of supramolecular interactions to build nanosystems with tailor-design structure and to achieve precisely controllable release, enhancing the treatment efficiency and reducing the potential toxicity. These systems can be applied in combination with external stimuli such as light, X-ray and heat to control materials responsiveness and for multimodality therapy. Furthermore, imaging units are incorporated to visualize nanomaterials in vitro and in vivo to provide a fast evaluation of their efficiency.

Scheme for multifunctional supramolecular interaction based polymeric nanomedicine

Reference [1] H. Zhu, H. Wang, B. Shi, L. Shuangguan, W. Tong, G. Yu,* Z. Mao,* F. Huang.* Nat. Comm. 2019, 10, 2412. [2] G. Yu, X. Zhao, J. Zhou, Z. Mao,* X. Huang, Z. Wang, B. Hua, Y. Liu, F. Zhang, Z. He, O. Jacobson, C. Gao, W. Wang, C. Yu,* X. Zhu, F. Huang,*, X. Chen*. J. Am. Chem. Soc. 2018, 140, 8005-8019. [3] G. Yu, Z. Yang, X. Fu, B. Yung, J. Yang, Z. Mao*, L. Shao, B. Hua, Y. Liu, F. Zhang, Q. Fan*, S. Wang, O. Jacobson, A. Jin, C. Gao, X. Tang, F. Huang*, X. Chen*. Nat. Comm. 2018, 9, 766.

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212

Zhihong Nie Fudan University

Zhihong Nie is a Professor in the State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science at Fudan University. He received his B.S. degree from Jilin University in 2000, M.S. degree from Changchun Institute of Applied Chemistry at Chinese Academy of Sciences in 2003 and Ph.D. degree from University of Toronto in 2008. After a two-year NSERC Postdoctoral experience with Professor George M. Whitesides at Harvard University, he joined the faculty in the Department of Chemistry and Biochemistry at the University of Maryland College Park in 2011 and was promoted to Associate Professor with tenure in 2017. He is the recipient of NSF CAREER Award, 3M Non-tenured Faculty Award, ACS PRF Doctoral New Investigator Award, etc. His research interests include molecular and nanoparticle self-assembly, biomedical imaging and delivery, programmable soft materials, and microfluidics.

4th CASNN Annual Meeting 2019

213 Engineering of hybrid nanovesicles for cancer theranostics Zhihong Nie†,*, Yijing Liu‡, Kuikun Yang‡, Xiaoyuan Chen‡

†State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, 2005 Songhu Rd, Shanghai 200438, China ‡Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health, Maryland 20892, United States Email: [email protected]

Nanoscale vesicles (e.g., liposomes, polymersomes) are capable of effectively encapsulating and delivering hydrophilic and/or hydrophobic compounds simultaneously. In the past decades, they have made a great clinical impact in controlled release of therapeutic drugs or vaccines. Inorganic nanoparticles (e.g., often have intrinsic optical, electrical, and magnetic properties that surpass their organic counterparts. To meet the rising need for better theranostic tools, reasonable efforts have been made to incorporate inorganic nanoparticles into the organic vesicular membranes to endow the system with new functionalities. The integration of inorganic nanoparticles is usually achieved by directly co-assembling amphiphilic lipids or block copolymers with hydrophobic nanoparticles, but this strategy suffers from limited size and shape of nanoparticles that can be loaded, poor control over the spatial organization of inorganic nanoparticles in the membrane, and inability of tuning the collective property of the hybrid vesicles. Recently, we have developed a strategy to fabricate hybrid nanovesicles with tailored physical and chemical properties through the self-assembly of block copolymer-grafted inorganic nanoparticles. This method allows us to readily tune the size, shape, and composition of the hybrid vesicles, and particularly, the collective optical and magnetic property of the hybrid vesicles by controlling the spatial organization of nanoparticles in the membrane. Both imaging and therapeutic agents can be efficiently encapsulated and retained in the hollow cavity of the vesicles with minimal leakage, compared with organic vesicles. The release of payload can be controlled in space and time by external triggers (e.g., near-infrared light, alternating magnetic field). We systematically assessed the potential of the hybrid vesicles as signal amplifier in ELISA-based cancer diagnosis, contrast agents in multimodality cancer imaging (e.g., photothermal, photoacoustic and magnetic resonance imaging), as well as delivery vehicles for cancer therapy (e.g., photodynamic therapy, chemodynamic therapy).

References [1] K.K. Yang,Y.J. Liu, Y. Liu, Q. Zhang, C.C. Kong, C.L. Yi, Z.J. Zhou, Z.T. Wang, G.F. Zhang, Y. Zhang, N.M. Khachab, X.Y. Chen, Z.H. Nie, Cooperative assembly of magneto-nanovesicles with tunable wall thickness and permeability for MRI-guided drug delivery, J. Am. Chem. Soc. 140(2018), 4666-4677. [2] H.H. Ye, K.K. Yang, J. Tao, Y.J. Liu, Q. Zhang, S. Habibi, Z.H. Nie, and X.H. Xia, An enzyme- free signal amplification technique for ultrasensitive colorimetric assay of disease biomarkers, ACS Nano 11 (2017), 2052–2059. [3] Y.J. Liu, X.Y. Yang, Z.Q. Huang, Y. Liu, L. Deng, C.L. Yi, X.L. Sun, S.Y. Zhang, N.M. Khachab, X.Y. Chen, Z.H. Nie, Magneto-plasmonic Janus vesicles for magnetic field- enhanced photoacoustic and magnetic resonance imaging of tumor, Angew. Chem. Int. Ed. 55(2016), 15297-15300. [4] Y.J. Liu, J. He, K.K. Yang, C.L. Yi, Y. Liu, L.M. Nie, N. M. Khashab, X.Y. Chen, Z.H. Nie, Folding up of gold nanoparticle strings into plasmonic vesicles for enhanced photoacoustic imaging, Angew. Chem. Int. Ed. 54(2015), 15916-20. [5] P. Huang, J. Lin, W.W. Li, P.F. Rong, Z. Wang, S.J. Wang, X.P. Wang, X.L. Sun, M. Aronova, G. Niu, R.D. Leapman, Z.H. Nie, X.Y. Chen, Biodegradable gold nanovesicles with ultra-strong plasmonic coupling effect for photoacoustic imaging-guided photothermal therapy, Angew. Chem. Int. Ed. 52 (2013), 13958–13964.

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214

Zhimou Yang College of Life Sciences, Nankai University

Zhimou Yang is a professor and director in Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University. Zhimou Yang was born 1978 in Guangdong Province, China. He received his BS from Nanjing University in 2001. He obtained his PhD in 2006 from the Hong Kong University of Science and Technology under the supervision of Professor Bing Xu. Before starting his independent research at Nankai University in March 2009, he was a postdoctoral fellow with Prof. Matthew Bogyo at Stanford Medical School. His research interests focus on biomedical applications of peptide-based hydrogels including hydrogels of drug-peptide amphiphiles for drug delivery, hydrogels of bioactive peptides for tissue engineering, and hydrogels as vaccine adjuvants, etc. He has published around 100 corresponding authored papers in the field of peptide self-assembly. He recently obtained the National Science Fund for Distinguished Young Scholars from National Natural Science Foundation of China in 2018. Lab homepage: http://yang-lab.org

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Supramolecular Nanofibers Mimicking IGF-1 Yuna Shang, Dengke Zhi, Kai Wang, Jie Gao, and Zhimou Yang

College of Life Sciences, Nankai University, Tianjin 300071, P. R. China Email: [email protected]

Introduction: Most of peptide segments in proteins are constrained into certain conformations, especially for bioactive peptides. However, when these peptides were separated from proteins, they failed to fold into their original conformations and therefore lost their functionalities. In this study, we introduced a simple but versatile strategy to control and constrain the secondary structure of bioactive peptides. We demonstrated that short peptides could be folded into different secondary structures (- helix or -sheet) by using different methods to trigger molecular self-assembly. The different secondary structures led to different nanostructures with totally different bioactivity. Most importantly, we found that when a peptide derived from insulin-like growth factor-I (IGF-1) folded into with - sheet in nanofibers, it showed a superior bioactivity than the IGF-1 protein. Meanwhile, the unassembled peptide and the -helical peptide in nanofibers showed a very poor bioactivity. Methods: Self-assembling peptide motif (Nap-FFG) were conjugated with IGF-1 derived peptide (IGF-1C). The resulting compound (Nap-FFG-IGF-1C, compound 1) self-assembled into two kinds of nanofibers through heating-cooling self-assembling and enzymatic-instructed self-assembling (EISA). The secondary structure of both nanofibers were characterized. The bioactivity of the nanofibers including cellular proliferation promotion and apoptosis inhibition were evaluated on HUVECs. The therapeutic efficacy of nanofibers were examined with mouse model of hind limb ischemia. Results: Compound 1 could self-assemble into nanofibers (Nanofiber 1) after heating-cooling process. CD results showed that the peptides in Nanofiber 1 mainly adopted -sheet secondary structure, while the free peptide of IGF-1C adopted a random-coil structure in solutions. Interestingly, compound 1 could also self-assembled into nanofibers (Nanofiber 2) through EISA, but CD results showed it adopted -helical structure in the nanofiber. The binding affinity of Nanofiber 1, Nanofiber 2 and IGF-1C to IGF-1 receptors were measured with SPR. Results showed that Nanofiber 1 exhibted the lowest dissociation constant (KD = 11.5 nM), which was much smaller than that of Nanofiber 2

(KD = 179.1 nM) and IGF-1C (KD = 321.6 nM). The high binding affinity led to stronger bioactivity of Nanofiber 1 over Nanofiber 2 and IGF-1C. Exposure to 10 nM of Nanofiber 1 could promote the proliferation of HUVEC and inhibit its apoptosis caused by H2O2, and the potency of Nanofiber 1 was even stronger than IGF-1 protein. However, Nanofiber 2 or IGF-1C did not show such superior bioactivity. Finally, when injected to ischemic limb of mouse, Nanofiber 1 also showed the best therapeutic efficacy among Nanofiber 2, IGF-1C and IGF-1 protein. Conclusion: We introduced a useful strategy to constrain peptides into different conformations, which may lead to the development of supramolecular nanomaterials mimicking biofunctional proteins.

References [1] Y. Shang, D. Zhi, G. Feng, Z. Wang, D. Mao, L. Liu, S. Guo, S. Zhang, S. Sun, K. Wang, D. Kong, J. Gao, Z. Yang, Supramolecular Nanofibers with Superior Bioactivity to IGF-1, Nano Lett. 19 (2019) 1560–1569. [2] C. Liang, D. Zheng, F. Shi, T. Xu, C. Yang, J. Liu, L. Wang, Z. Yang, Enzyme assisted peptide folding, assembly and anti-cancer property, Nanoscale, 9 (2017) 11987–11993. [3] J. Zhan, Y. Cai, S. Ji, S. He, Y. Cao, D. Ding, L. Wang, Z. Yang, Spatiotemporal Control of Supramolecular Self-Assembly and Function, ACS Appl. Mater. Interf., 9 (2017) 10012–10018.

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216

Zhiqiang Cao, Ph.D.

Wayne State University

Prof. Zhiqiang Cao received his Ph.D. in Chemical Engineering from the University of Washington in 2011 under the guidance of Prof. Shaoyi Jiang. He was a research fellow in Prof. Robert Langer’s lab at David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, and the Department of Anesthesiology at Children’s Hospital Boston and Harvard Medical School from 2011 to 2012. He received his B.Eng. in Polymer Materials and Engineering and M.Eng. in Biomedical Engineering from Tianjin University, China in 2004 and 2007, respectively. He joined the Department of Chemical Engineering and Materials Science at Wayne State University in January 2013 and was promoted to Associate Professor with tenure in April 2017. His research is supported by National Science Foundation (NSF), National Institutes of Health (NIH) and multiple programs from Juvenile Diabetes Research Foundation (JDRF). He receives the 2016 NIH NIDDK Type 1 Diabetes Pathfinder Award (DP2). His lab uses a multidisciplinary approach, to study new materials and their translational applications in healthcare and biomedical engineering.

4th CASNN Annual Meeting 2019

217 Zwitterionic polymer surfactants for drug delivery

Zhiqiang Cao

Chemical Engineering and Materials Science, Wayne State University, Detroit, Michigan, USA Email: [email protected]

Zwitterionic polymers emerged as a new generation of materials with excellent non-fouling properties. Their novel use as surface coatings has shown efficient resistance to the adhesion from proteins, cells, and full blood. When the materials were contacted with tissues such as through subcutaneous implantation, a level of tissue compatibility was achieved by resisting foreign body reaction with surrounding tissues. When the materials were contacted with blood such as serving a surface coating for nanoparticles, blood compatibility was achieved resulting long blood circulation time of the modified nanoparticles. These excellent properties were attributed to the unique superhydrophilicity of these polymers providing strong hydration effects. Our lab focuses on exploring novel zwitterionic polymer materials, and studying their translational potentials in healthcare. I will highlight our zwitterionic-based technology for nanoparticles and nanomedicine. In particular, I will introduce a so-called sharp contrast zwitterionic polymer surfactant system. Each surfactant molecule composes of a superhydrophilic zwitterionic polymer block and a superhydrophobic lipid block. The polarity contrast between the two domains is drastically “sharper” than most conventional surfactant molecules. We will discuss the special synthetic route that led to the reaction between the two polarity distinct blocks to form the sharp contrast surfactant. We will further discuss the unique behavior of this sharp contrast surfactant in stabilizing drug payloads in blood serum and an improved drug delivery outcome.

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Zhugen Yang Cranfield Water Science Institute, Cranfield University, UK Email: [email protected] Web: www.zhugenyang.com Dr Zhugen Yang is Lecturer (Assistant Professor, UK tenure) and NERC Fellow, heading sensors lab at Cranfield University. Dr Yang started his independent academic career as Lecturer at the University of Glasgow’s James Water School of Engineering in 2018 before relocating to Cranfield recently. He received a prestigious UKRC Research Fellowship in 2017 to establish a research group on advanced sensing for Water-Environment-Health nexus. He was EU Marie Curie Fellow at the University of Bath after completing a Postdoc at the University of Cambridge. He received his PhD from University of Lyon (Ecole Centrale) in France, MSc (SYSU) and BEng (HIT) in China.

He is a multidisciplinary researcher, mainly focusing on low-cost, rapid and point-of-use sensors and devices for biomedical diagnostics (e.g. infectious disease and cancer), environmental science (e.g. microbial contamination in drinking water), public health (e.g. illicit drug of abuse with wastewater analysis). His research has been sponsored with over ~£1M by UK and international research council. The research outputs led to 40 referred articles (such as PNAS, ACS sensors, Anal Chem, ES&T, Water Res) and one book on microarray technology.

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219 Paper-origami device enabling low-cost and rapid microbial analysis Yuwei Pan1, Kang Mao1, Franziska Tuerk1,2, Zhugen Yang1,2

1School of Water, Energy and Environment, Cranfield University, Cranfield, MK43 0AL, UK 2School of Engineering, University of Glasgow, Glasgow, G12 8LT, UK Email: [email protected]

Microbial detection is of significant importance for both biomedical diagnostics (e.g. infectious disease) and environmental analysis (e.g. microbial contamination in drinking water). This has traditionally been performed by culturing and typing the pathogens, however, these procedures often take several days. Molecular approaches (such as polymerase chain reaction (PCR) detecting genetic markers) will deliver faster turn-around times (< 1 hour) than culture-based methods, but currently require centralised facilities and skilled personnel to perform the assays and interpret results. There is, therefore, an urgent need to develop rapid and sensitive platforms that can provide rapid analysis of microbial both for biomedical diagnosis and environmental analysis. Here we report on a low-cost, deployable paper-based biosensor device for rapid analysis of microbes. Using a paper-microfluidic sensor with isothermal amplification technologies, we have demonstrated rapid, sensitive and easy-to- use sample-to-answer testing devices for rapid infectious disease of bovine, which was also field tested in India. Pathogen DNA was amplified with loop-mediated isothermal amplification (LAMP) and detected fluorescently, enabling a promising genetic DNA (from 10 to 100 copies per reaction) to be measured. Experimental results show that the data from our paper-origami device are able to be collected as a fluorescence signal either visually, using a low-cost hand-held torch, or digitally with a mobile-phone camera (Figure 1). We carried on double-blind tests for the semen samples collected from elite bulls at a germplasm centre, as a demonstrator for a low cost, user-friendly point-of-care sensing platform, for in-the-field testing in resource-limited regions, indicating for the first of time demonstration of the application of paper-origami devices for the diagnosis multiple infectious diseases from semen samples. We also show this device for the rapid test of microbial contaminations in drinking water, with a flexible sampling enrichment strategy with magnetic beads equipped on a syringe, enabling rapid analysis of microbial contamination in drinking water in low resource setting, and to address global water contamination issues.

(I) Unfolded paper device (II) Plastic plate

1 P 2 N 3

Detection after amplification 3mm

1 P 2

N 3 Figure 1 Paper-origami device for the multiplexed visual detection of pathogens

Reference [1] J. Reboud, G. Xu, Gretter, A, Z. Yang et al. Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities. PNAS 116 (2019) 4834-4842. [2] Z. Yang et al. Rapid Veterinary Diagnosis of Bovine Reproductive Infectious Diseases from Semen Using Paper-Origami DNA Microfluidics. Acs Sensors 3 (2018): 403-409. [3] Z. Yang, et al. "Monitoring Genetic Population Biomarkers for Wastewater-Based Epidemiology. Anal Chem 89(2017): 9941-9945.

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221 Abstracts of Rising Star Forum

222 Cell-based nanoparticles for targeted immunomodulating Qingle Ma, Chao Wang*

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon- based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China Email: [email protected]

Immunotherapy utilizes the patient’s own immune system to fight against disease. For example, cancer immunotherapy has been proved successful to treat cancer, remarkably improving the therapy efficacy in clinic. However, some limitations still need to be addressed, such as low response rate and immune-related adverse events (irAEs) caused by off-targeting. Therefore, new target strategy should be developed for improve the immunotherapy.[1] In recent years, a variety of novel biomaterials and strategies have been reported to targeted deliver therapeutics for immunotherapy. Among them, cell and cell-based nanoparticles, such as red blood cells, platelets, cell-derived nanovehicle and exosomes, as a kind of important bio-nanomaterial that has been extensively studied for drug delivery. Inspired by the excellent inflammatory targeting ability of platelets, We have designed a platelet- based platform that coupled the monoclonal antibody against programmed-death ligand 1(aPD-L1) to surface of platelets. The antibody-coupled platelets could effectively target incompletely resected tumor after surgery, trigger the release of aPD-L1 upon the platelets activation, and remarkably prevent tumor recurrence after surgery, reducing the risk of cancer recurrence.[2] Moreover, it also expanded the application of the platelet-based delivery strategy in other types of local therapies including thermal ablation PDT, HIFU and radiotherapy[3] (Figure 1). In our recent research, cell- based nanoparticles have been targeted to areas of inflammation and atherosclerotic plaque as well.

Figure 1. Schematic illustration of aPDL1-conjugated platelets and therapeutic mechanism to treat residue tumor after thermal ablation[3].

References [1] Q. Fan, Z.P. Chen, C. Wang, Z. Liu, Toward Biomaterials for Enhancing Immune Checkpoint Blockade Therapy, Advanced Functional Materials, 28 (2018) 1802540. [2] C. Wang, W. Sun, Y. Ye, Q. Hu, H.N. Bomba, Z. Gu, In situ activation of platelets with checkpoint inhibitors for post-surgical cancer immunotherapy, Nat. Biomed. Eng., 1 (2017) 0011. [3] X. Han, J. Chen, J. Chu, C. Liang, Q. Ma, Q. Fan, Z. Liu, C. Wang, Platelets as platforms for inhibition of tumor recurrence post-physical therapy by delivery of anti-PD-L1 checkpoint antibody, Journal of Controlled Release, (2019).

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223 In vivo cooperative self-assembling porphyrin nanostructure for enhanced phototherapy Chengchao Chu, Gang Liu*

Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China E-mail: [email protected] Introduction: Our previous study implied that Mn(II) ion could induce the self-assembly of sinoporphyrin sodium (DVDMS) in a rapid time, leading to the enhancement of photodynamic therapy

(PDT) and photothermal therapy (PTT). In addition, the manganese dioxide (MnO2) could be decomposed in the tumor environment due to the interaction with H2O2 (in acid solution). Meanwhile, the produced oxygen (O2) could benefited for the PDT, and the released Mn(II) ion could induce the self-assembly procedure. Hereby, an in vivo cooperative self-assembling strategy was constructed to the enhanced phototherapy. Methods: i)The RGD modified Human Serum Albumin (RGD-HSA) was synthesized, and then mixed with DVDMS; ii) afterward, the MnO2 was prepared by mixing the aqueous solutions of KMnO4 and poly(allylaminehydrochloride); iii) finally, the MnO2 was added to the above mixture, preparing the

RGD-HSA/DVDMS/MnO2 nano-composites (R-HDM).

Figure 1 TEM of the MnO2 (A), R-HDM (B) and R-HDM+H2O2 (C). The Zeta-potential (D) and UV- Vis study (E) of the prepared nanostructures. (F) Cell viability at different dosages of the RGD-HSA

(a), DVDMS (b), MnO2 (c) and R-HDM (d). (G) Phototherapy of DVDMS (a), RGD-HSA/DVDMS (b) and R-HDM (c). (H) In vivo fluorescence imaging after injection of R-HDM.

Results and Conclusion: The prepared MnO2 was homodisperse nanoparticle structure with diameters of ~ 5 nm (Figure 1A), and then assembled into irregular nanosheet of the R-HDM (Figure

1B). After reacted with H2O2, the MnO2 in the R-HDM was decomposed and the R-HDM re- assembled into irregular three-dimensional nanostructure (Figure 1C). And, the re-assembled nanostructure possessed enhanced phototherapy effect. The Zeta-potential (Figure 1D) and the UV-Vis study (Figure 1E) also confirmed these procedures. The R-HDM possessed no obvious cytotoxicity (Figure 1F), and showed enhanced photo-toxicity than the DVDMS and RGD-HSA/DVDMS (Figure 1G). In addition, the in vivo fluorescence imaging demonstrated the good tumour targeting effect (Figure 1H). In conclusion, our prepared R-HDM could enabled the in vivo re-assembly strategy and showed good phototherapy efficiency to the tumor.

References [1] C. Chu, H. Lin, H. Liu, X. Wang, J. Wang, P. Zhang, H. Gao, C. Huang, Y. Zeng, Y. Tan, G. Liu, X Chen, Tumor microenvironment-triggered supramolecular system as an in situ nanotheranostic generator for cancer phototherapy, Adv. Mater. 29 (2017) 1605928.

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224 Tumor-penetrating graphene based nanosystem for high efficient sonodynamic therapy Yingxue Zhang1, Jiming Xu1, Yikun Wang1, Tingting Li1, 2, Hong Yang1, 2 Yiyao Liu1,2, and Chunhui Wu1, 2*

1Department of Biophysics, School of Life Science and Technology, 2Center for Information in Biology, University of Electronic Science and Technology of China, Chengdu 610054, China *E-mail: [email protected]

Currently, sonodynamic therapy (SDT), as an alternative way of photodynamic therapy, is gradurally being attached enormous attention due to the advantages of high tissue penetration of ultrasound and the multiple anticancer mechanisms of sonosensitzers under ultrasonic activation [1]. And various ultrasound triggered nanocomplex greatly improved the efficiency of SDT. However, the complex tumor microenvironment is still a huge hurdle. Due to the vascular dyfunction of tumor, nanoparticles could only enter tumor tissue via the enhanced permeability and retention effect and then remain near the blood vessels [2]. To develop a highly efficient and penetrating nanosystem for SDT, this study adapted functionalized graphene oxide (GO) as a skeleton to load the sonisensitizer Chlorin e6 (Ce6) and then modify it with tumor homing and penerating ligand tLyP-1 to specifically target NRP receptors and then direct the nanocomplex to the tumor center. The yielded nanocomplex (GPt/Ce6) was about 250 nm as determined by DLS. The spectroscopic results showed that the drug loading rates of tLyP-1 and Ce6 were 43% and 48%, respectively. Under activation by ultrasound, GPt/Ce6 had excellent ROS production efficiency. The in vitro biological results showed that GPt/Ce6 had a deep penetration into the tumor sphere. Our results demonstrated the great promise of this type of penetrating nanosystem for high efficient tumor SDT. (Acknowledgements: We greatly acknowledged the support of the National Natural Science Foundation of China (81471785, 81671821, 31470959, 11772088, 31700811, 11802056, 31800780), the Basic Research Program of Sichuan Science and Technology (2017JY0217, 2017JY0019), and the Fundamental Research Funds for the Central Universities (ZYGX2016Z001).

Scheme 1. Schematic illustration of the fabrication of GPt/Ce6 and its high efficient cancer SDT.

References [1] R. G. Liu, Q.Y. Zhang, Y. H. Lang, Z. Z. Peng, L.B. Li, Sonodynamic therapy, a treatment developing from photodynamic therapy, Photodiagn. Photodyn. 19(2017)159–166. [2] X. Q. Qian, Y. Y. Zheng, Y. Chen. Micro/nanoparticle-augmented sonodynamic therapy (SDT): breaking the depth shallow of photoactivation, Adv. Mater. 28(2016) 8097–8129.

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225 Theranostic nanoparticles with two-photon AIE imaging and tumor- programmed responsiveness for efficient cancer treatment Gaocan Li, Boxuan Ma, Weihua Zhuang, Hong Xu, Li Yang and Yunbing Wang*

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China. *Corresponding authors. Email: [email protected] (Y. Wang) As a potential strategy for cancer diagnosis and therapy, theranostic nanoparticles exhibit reduced side effect, promising bioimaging ability and great drug utilization. However, further work is still required for deep tissue bioimaging and accurate drug delivery at tumor tissue[1]. Organic two-photon fluorophore, specializing in strong penetration ability, provides a feasible strategy for the deep tissue imaging[2]. What’s more, taking advantage of the specific microenvironment of tumor tissue, the nanocarriers with hierarchical responsiveness can offer a tumor-programmed drug release for the accurately efficient tumor inhibition[3]. Herein, a hierarchically responsive nanoparticle (HRNP) with two-photon aggregation induced emission (AIE) has been constructed with gemcitabine (GEM) loaded. While under the two-photon excitation at 800 nm, HRNPs reveal a deeper tissue bioimaging up to 150 μm compared to the traditional single-photon fluorophore (Fig. 1A). Furthermore, as compared to the free GEM and single responsive nanoparticles (SRNPs), HRNPs can orderly respond to the tumor extracellular pH (~6.8) and the intracellular reactive oxygen species (ROS), which achieves a tumor- programmed accurate drug release, thereby a better antitumor effect (Fig. 1B). Therefore, HRNPs can be a potential candidate for tumor theranostic applications.

Figure 1. Two-photon CLSM images of the kidney tissues after injection of HRNPs for 12 h (A). The scale bars were 100 μm. The tumor volume variation of the mice treated with free GEM, SRNPs, HRNPs and saline over 21 days (B) (**p < 0.01, *p < 0.05). (Gray arrows indicated drug dosing regimen with 5 mg GEM/kg body weight). Keywords: two-photon, pH responsive, ROS responsive, drug delivery Acknowledgement: Financial support from the National NSF of China (No. 21502129) and the National 111 Project of Introducing Talents of Discipline to Universities (No. B16033).

References [1] D. Peer, J. M. Karp, S. Hong, O. C. Farokhzad, R. Margalit, R. Langer, Nanocarriers as an emerging platform for cancer therapy, Nat Nanotech. 2 (2007) 751-760. [2] F. Helmchen, W. Denk, Deep tissue two-photon microscopy, Nat. Methods 2 (2005) 932-940. [3] Q. Sun, Z. Zhou, N. Qiu, Y. Shen, Rational design of cancer nanomedicine: nanoproperty integration and synchronization, Adv. Mater. 29 (2017) 1606628.

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226 Camouflaging bacteria by coating with erythrocyte membranes Jinyao Liu*

Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai 200127 Email: [email protected]

Microbes are ubiquitous and are essential components of ecosystems, in particular playing critical roles in the maintenance of mammalian homeostasis and host health1. Thanks to their unique characteristics including disease site targeting specificity, rapid proliferation and genetic manipulation, bacteria have been extensively utilized for therapy, diagnosis and bioimaging2-5. However, clinical translation of bacteria for these applications has been largely restricted by their unavoidable side effects caused by immunogenicity and low treatment efficacies resulted from rapid clearance by the reticuloendothelial system (RES) before colonizing specific target sites6,7. Here we show the camouflage of bacteria by wrapping with cell membranes, giving bacteria that show slow elimination by macrophages, almost unchanged inherent bioactivities and low accumulation in normal organs, and generate only a low inflammatory response (Figure 1). Our findings are supported by evaluation in mice models and ultimately demonstrate the potential of cell membrane coated bacteria to serve as efficient tumour targeting therapeutics. This strategy is applicable to different strains such as gut microbes and therapeutic bacteria and suitable for coating with diverse cell membranes including platelet, macrophage, neutrophil and cancer cell membranes. We anticipate the camouflage of bacteria by wrapping with cell membranes to be a versatile approach for the preparation of biologically functional bacteria with improved safety and enhanced treatment efficacy.

References [1] G. E. Kaiko, T. S. Stappenbeck, Host-microbe interactions shaping the gastrointestinal environment. Trends. Immunol. 35 (2014) 538-548. [2] T. Danino, et al. Programmable probiotics for detection of cancer in urine. Sci. Transl. Med. 7 (2015) 289ra284. [3] R. W. Bourdeau, et al. Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts. Nature 553 (2018) 86-90. [4] S. E. Fritz, et al. A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma. Vet. Med. Sci. 2 (2016) 179-190. [5] R. Mercado-Lubo, et al. A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours. Nat. Commun. 7 (2016) 12225. [6] W. Chen, et al. Bacteria-Driven Hypoxia Targeting for Combined Biotherapy and Photothermal Therapy. ACS Nano 12 (2018) 5995-6005. [7] J. F. Toso, et al. Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J. Clin. Oncol. 20 (2002) 142-152.

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227 “Self-promoted” nanoparticles for brain metastasis targeting drug delivery Tongtong Miao, Qian Guo, Xiufeng Ju, Liang Han

Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China Email: [email protected]

Introduction: Brain metastasis is the most common intracranial tumor and mostly displays multifocal, co-opting, and infiltrative growth. Because of the brain location and the growth pattern, it is one of the most difficult malignancies to treat. Chemotherapy, which is often effective against peripheral tumors, offers promising treatment option. Nanotechnology-based drug delivery strategies have been researched to improve the efficiency of systemic drug delivery to brain metastases. However, this efficiency is extremely limited due largely to the blood-brain barrier (early micrometastases) and the blood-brain tumor barrier (advanced large metastases). For the blood-brain barrier, low transcytosis is increasingly thought a crucial factor in restricting the permeability besides tight junction. The blood- brain tumor barrier can paracellularly permit drug penetration through disrupted tight junctions and augmented fenestrations. However, the barrier leakage in most brain metastases is not enough to reach therapeutically effective concentrations.

Methods: Angiopep-2 (brain targeting ligands) ligates the low density lipoprotein receptor related protein 1 (receptor) on brain microvascular endothelial cells to drive transcytosis to enter brain. Statins-loaded Angiopep-2-anchored nanoparticles were designed to raise specially receptor expression on brain microvascular endothelial cells to surmount the low transcytosis of the blood-brain barrier. Lexiscan- loaded chlorotoxin-modified nanoparticles and minoxidil-loaded hyaluronic acid-tethered nanoparticles were designed to release vasoactive agents to selectively act on the blood-brain tumor barrier for efficient crossing.

Results and Conclusion: Statins-loaded Angiopep-2-anchored nanoparticles can selectively up-regulate receptor expression on both brain microvascular endothelial cells and brain metastatic tumor cells, efficiently and self- promotingly penetrate through the blood-brain barrier and target brain metastases through Angiopep-2 mediated endocytosis and statins induced receptor up-regulation [1]. Lexiscan-loaded chlorotoxin- modified nanoparticles can release lexiscan to open tight junction of the blood-brain tumor barrier for more nanoparticles’ transport [2]. Minoxidil-loaded hyaluronic acid-tethered nanoparticles can release minoxidil to boost transcytosis and down-regulate tight junction protein to efficiently and specially surmount the blood-brain tumor barrier [3]. Both nanoparticles selectively deliver anti-cancer drug to brain metastatic lesions, while sparing normal brain cells and were capable of mediating efficient chemotherapy.

References: [1] Q. Guo, Q. Zhu, T. Miao, J. Tao, X. Ju, Z. Sun, H. Li, G. Xu, H. Chen, L. Han, LRP1-upregulated nanoparticles for efficiently conquering the blood-brain barrier and targetedly suppressing multifocal and infiltrative brain metastases, J. Control. Release 303 (2019) 117–129. [2] L. Han, D. K. Kong, M. Q. Zheng, S. Murikinati, C. Ma, P. Yuan, L. Li, D. Tian, Q. Cai, C. Ye, D. Holden, J. H. Park, X. Gao, J. L. Thomas, J. Grutzendler, R. E. Carson, Y. Huang, J. M. Piepmeier, J. Zhou, Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging, ACS Nano 10 (2016) 4209-4218. [3] T. Miao, X. Ju, Q. Zhu, Y. Wang, Q. Guo, T. Sun, C. Lu, L. Han, Nanoparticles surmounting blood-brain tumor barrier through both transcellular and paracellular pathways to target brain metastases, Adv. Funct. Mater. 2019, doi: 10.1002/adfm. 1900259.

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228 Ionic functional polyester and their application as nanocarriers for Anti- ctumor drugs Liuchun Zheng1, Qiyong Mei2*, Shaohua Wu1, Jiaxu Li1,3, Chuncheng Li1*, Haihua Xiao1

1CAS Key Laboratory of Engineering Plastics, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China; 2 Department of Neurosurgery, Changzheng Hospital, the Second Military Medical University, Shanghai 200003 China; 3 University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China; E-mail: [email protected] or [email protected]

The ions, including cations, anions and zwitterions have been applied to modify polyester, and the resulting sulfonate polyester, -NH2, –COOH and zwitterionic polyesters can self- assembled or co-assembled to micelles. The prepared micelles can be applied as the anti-tumor drug-loaded nanocarriers to improve the biocompoatibility, prolong the circulation time of the drugs in the blood and improve the stability of the drug loading due to the good biocompatibility and antifouling properties of anions and zwitterions. PBS-g-MPA/CS-bi-PEG micelles show a high drug-loading content of 10.2% and entrapment efficiency of 68%. DOX loaded micelles shows a pH triggered released profile with significant cytotoxicity toward cancer cells while the blank PBS-g-MPA/CS-bi-PEG micelles possessed excellent biocompatibility. Impressively, when use as multifunctional drug delivery vehicles, the poly(butyl fumarate-polyethylene glycol fumarate)-cysteine100%-Pt-C16 nanoparticles not only exhibit pH- and reduction-responsive drugs release properties, but also provide high ovarian cancer treatment efficiency in vitro, resulting in evidently decreased IC50 values of cisplatin As compared to cisplatin, the IC50 value of the nanoparticles sensitizes A2780 cells has been decreased by 2.35 fold.

References [1] Zhang et al, Zwitterionic gel encapsulation promotes protein stability, enhances pharmacokinetics, and reduces immunogenicity. PNAS 2015, 112:12046-12051. [2] Wu et al, Grafted Copolymer Micelles with pH Triggered Charge Reversibility for Efficient Doxorubicin Delivery, J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 2036–46 [3] Wu et al, A facile and versatile strategy to efficiently synthesize sulfonated poly(butylene succinate), self-assembly behavior and biocompatibility, Polym. Chem., 2015, 6, 1495-1501.

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229 Aggregation-induced emission materials with brighter fluorescence and narrower emission band by light-harvesting strategy Xin Zhu, Li-Ya Niu*, Qing-Zheng Yang

College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China Email: [email protected]

Aggregation-induced emission luminogens (AIEgens) have been demonstrated as alternatives to traditional ACQ fluorophores and attracted increasingly attentions in recent years.[1] However, most AIEgens exhibit broad emission spectra with the full width at half-maxima (FWHM) over 100 nm, and creation of narrow-band AIE materials has been in high demand but challenging. Based on light- harvesting strategy, we developed supramolecular polymeric AIE materials, including nanoparticles, microfibers, and thin films, with brighter fluorescence and narrower emission band than conventional AIEgens. These AIE materials consist of tetraphenylethylene (TPE) as antenna chromophores and borondipyrromethene (BODIPY) and as energy acceptors based on quadruple hydrogen-bonded monomers. The efficient energy transfer fromTPE to the BODIPY enabled up to 6-fold enhanced fluorescence intensity and narrowed emission band with FWHM decreasing from 148 to 32 nm. The highly fluorescent nanoparticles were successfully applied for in vitro and in vivo fluorescence and chemiluminescence imaging.[2]

References [1] J. Mei, N.L.C. Leung, R.T.K. Kwok, J.W.Y. Lam, B.Z. Tang, Aggregation-Induced Emission: Together We Shine, United We Soar!, Chem. Rev., 115 (2015) 11718-11940. [2] X. Zhu, J.X. Wang, L.Y. Niu, Q.Z. Yang, Aggregation-Induced Emission Materials with Narrowed Emission Band by Light-Harvesting Strategy: Fluorescence and Chemiluminescence Imaging, Chem. Mater., 31 (2019) 3573-3581.

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230 Preparation and biomedical application of mcro/nano covalent organic polymers/frameworks Chunling Hua, b, Sainan Liua, b, Maolin Panga, b*

a State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China b University of Science and Technology of China, Hefei 230026, P. R. China Email: [email protected]

Attributed to the high surface areas, excellent stability and tunable pore structures, covalent organic polymers/frameworks (COPs or COFs) have attracted great attention across diverse research fields [1,2]. However, size and shape controlled growth of nanoscale COPs or COFs is still scarce, meanwhile, rendering these materials for in vivo biomedical applications is just in its early stage. Herein, monodispersed COPs or COFs nanoparticles such as nanometalated COP, porphyrin- containing Tph-Dha-COP, TpPa-1 COF etc., were successfully prepared by a facile solution-based synthesis method at room temperature [3-10]. Due to the good biocompatibility, high drug loading efficiency, excellent photothermal and photodynamic effect, the in vitro and in vivo evaluation indicated that these nanoparticles could be used as ideal drug carriers or photosensitizers for photothermal and/or photodynamic cancer therapy with high antitumor efficacy. This report provides an efficient approach to fabricate nano COPs or COFs, and also demonstrates the great potential of these materials for biomedical applications.

References [1] C.S. Diercks, O.M. Yaghi, The atom, the molecule, and the covalent organic framework, Science 355 (2017) eaal1585. [2] P.J. Waller, F. Gandara, O.M. Yaghi, Chemistry of covalent organic frameworks, Acc. Chem. Res. 48 (2015) 3053-3063. [3] C. Hu, Z. Zhang, S. Liu, X. Liu, M. Pang, Monodispersed CuSe Sensitized Covalent Organic Framework Photosensitizer with an Enhanced Photodynamic and Photothermal Effect for Cancer Therapy, ACS Appl. Mater. Interfaces (2019) DOI:10.1021/acsami.1029b08394. [4] S. Liu, Y. Liu, C. Hu, X. Zhao, P. Ma, M. Pang, Boosting the antitumor efficacy over a nanoscale porphyrin-based covalent organic polymer via synergistic photodynamic and photothermal therapy, Chem. Commun. 55 (2019) 6269-6272. [5] Y. Liu, C. Hu, S. Liu, X. Zhao, M. Pang, J. Lin, Ion-Doped Poly(2-Nitro-1,4-Phenylenediamine) Hollow Nanospheres for Photothermal Therapy, ACS Appl. Nano Mater. 2 (2019) 2106-2111. [6] Y. Shi, S. Liu, Y. Liu, C. Sun, M. Chang, X. Zhao, C. Hu, M. Pang, Facile Fabrication of Nanoscale Porphyrinic Covalent Organic Polymers for Combined Photodynamic and Photothermal Cancer Therapy, ACS Appl. Mater. Interfaces 11 (2019) 12321-12326. [7] S. Liu, C. Hu, Y. Liu, X. Zhao, M. Pang, J. Lin, One-pot synthesis of DOX@covalent organic framework with enhanced chemotherapeutic efficacy, Chem. Eur. J. 25 (2019) 4315-4319. [8] Z. Xie, X. Cai, C. Sun, S. Liang, S. Shao, S. Huang, Z. Cheng, M. Pang, B. Xing, A.A.A. Kheraif, J. Lin, O2-Loaded pH-Responsive Multifunctional Nanodrug Carrier for Overcoming Hypoxia and Highly Efficient Chemo-Photodynamic Cancer Therapy, Chem. Mater. 31 (2019) 483-490. [9] C. Hu, Y. Shi, C. Sun, S. Liang, S. Bao, M. Pang, Facile Preparation of Ion-Doped Poly(p- phenylenediamine) Nanoparticles for Photothermal Therapy, Chem. Commun. 54 (2018) 4862-4865. [10] Y. Shi, X. Deng, S. Bao, B. Liu, B. Liu, P. Ma, Z. Cheng, M. Pang, J. Lin, Self-Templated Stepwise Synthesis of Monodispersed Nanoscale Metalated Covalent Organic Polymers for In Vivo Bioimaging and Photothermal Therapy, Chem. Asian J. 12 (2017) 2183-2188.

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231 Photothermal nano-agent based on naturally occurring biliverdin for cancer phototheranostics Ruirui Xing, Kaiwei Chen, Xuehai Yan

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, 1 North 2nd Street, Zhongguancun, Haidian District, Beijing, PR China 100190 Email: [email protected]

Biliverdin (BV) is uniquely advantageous because it is spontaneously occurring, NIR-absorbing, nontoxic, non-fluorescent, endogenously produced and can be further degraded through a clear metabolic mechanism, along with the highly evaluation of its biological activity. However, to be powerful photothermal agents, the limited inherent instability and easily oxidability of BV must be overcome. Inspired by the intrinsic protein compatibility and metal-chelating advantages of BV in naturally organized assemblies, here, we demonstrate the use of histidine containing peptide to actively regulate the self-assembling of BV, thereby controlling its non-covalent assembly. Following, the metallic ion self-assembly was smartly manipulated to the fabrication of photothermal nanosystem. We show that the naturally-occurring bile pigment based photothermal nano-agents are extremely stable, biocompatible, NIR absorbing and have an efficient photothermal conversion. We provide the first report of BV nanoparticles as photothermal agents. Besides, the tumor visualization by photoacoustic imaging (PAI) combining magnetic resonance imaging (MRI) and antitumor efficacy by photothermal therapy (PTT) were achieved. Bile pigment merged with peptide and functional metal ions provided an advanced strategy for the construction of novel photothermal nano-agents, holding promise for applications in multifunctional imaging and PTT on tumors.

References [1] R. Xing, Q. Zou, C. Yuan, L. Zhao, R. Chang, X. Yan, Self-assembling endogenous biliverdin as a versatile near-infrared photothermal nanoagent for cancer theranostics, Adv. Mater. 31 (2019) 1900822. [2] S. Li, Q. Zou, Y. Li, C. Yuan, R. Xing, X. Yan, Smart peptide-based supramolecular photodynamic metallo-nanodrugs designed by multicomponent coordination self-Assembly, J. Am. Chem. Soc. 140 (2018) 10794-10802. [3] J. Wang, K. Liu, R. Xing, X. Yan, Peptide self-assembly: thermodynamics and kinetics, Chem. Soc. Rev. 45 (2016) 5589-5604.

4th CASNN Annual Meeting 2019

232 Diselenide-pemetrexed assemblies combine cancer immunotherapy with radiotherapy and chemotherapy Tianyu Li, Huaping Xu

Department of Chemistry, Tsinghua University, Beijing, 100084, People’s Republic of China Email:[email protected]

Introduction Immunotherapy has emerged as a promising new approach for cancer treatment. However, clinically available drugs have been limited until recently, and the antitumour efficacy of most cancer immunotherapies still needs to be improved. Herein, diselenide-pemetrexed assemblies were developed to combine cancer immunotherapy with radiotherapy and chemotherapy. Under γ-radiation, diselenide was oxidized to seleninic acid, which suppressed the expression of human leukocyte antigen E (HLA-E) in cancer cells, thus activating the immunoactivity of nature killer (NK) cells. The chemotherapeutic drug-pemetrexed could be simultaneously released. In this way, cancer immunotherapy is combined with radiotherapy and chemotherapy, which reveals a new strategy for combination therapy in cancer treatment.

Methods and Results We utilized pemetrexed, a clinically available chemotherapy drug, to self-assemble with cytosine- containing diselenides (Cyt-SeSe-Cyt) through hydrogen bonds. The prepared diselenide-pemetrexed (Pem/Se) self-assemblies combined cancer immunotherapy with radiotherapy and chemotherapy. Diselenide bonds were sensitive to γ-radiation. Under γ-radiation, diselenides were transformed into seleninic acid, demonstrated with 77Se-NMR, ESI-MS, and XPS. The assemblies collapsed at the same time, resulting in the release of pemetrexed, which was demonstrated with TEM, and DLS. Cell viability experiments exhibited good anticancer activity of Pem/Se against MDA-MB-231 cells, which was further enhanced under mild γ-radiation. The combination of chemotherapy and radiotherapy resulted from the release of pemetrexed promoted by γ-radiation. The cancer immunoactivity of seleninic acid was demonstrated by western blotting. Pem/Se incorporating with γ- radiation could inhibit the expression of HLA-E and induce higher death rates of cancer cells co- cultured with NK92 cells. In addition, the combination therapy exhibited high antitumor efficacy and low side effects in MDA-MB-231 xenograft tumour-bearing BALB/c-nude mice.

Conclusion The combination of cancer immunotherapy with radiotherapy and chemotherapy was achieved using diselenide-pemetrexed assemblies. Under a γ-radiation of 5 Gy, diselenide bonds could be cleaved to form seleninic acid, which activated cancer immunity of NK cells via inhibiting the expression of HLA-E protein. Pemetrexed was also released under γ-radiation, which improved the anticancer activity. The combination therapy exhibited good antitumour efficacy and low side effects. The development of Pem/Se assemblies revealed the great potential of selenium compounds in cancer immunotherapy and provide a novel strategy for combination cancer therapy.

References [1] H. Xu, W. Cao, X. Zhang, Acc. Chem. Res. 46 (2013) 1647-1658. [2] T. Li, M. Smet, W. Dehaen, H. Xu, ACS Appl. Mater. Interfaces 8 (2016) 3609-3614. [3] T. Li, F. Li, W. Xiang, Y. Yi, Y. Chen, L. Cheng, Z. Liu, H. Xu, ACS Appl. Mater. Interfaces 8 (2016) 22106-22112. [4] T. Li, W. Xiang, F. Li, H. Xu, Biomaterials 157 (2018) 17-25.

4th CASNN Annual Meeting 2019

233 Tumor exosome-based nanoparticles for efficient drug delivery Tuying Yong, Xiaoqiong Zhang, Nana Bie, Lu Gan, Xiangliang Yang National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China E-mail: [email protected]; [email protected]

Developing efficient drug delivery carriers for extraordinary tumor targeting remains a major challenge in cancer chemotherapy. Target agents, such as target antibody, peptides or other biomolecules, are widely used for targeting delivery of anticancer drugs[1]. However, enhanced immune-elimination and limited targeting ability restrict further application[2]. Biomimetic nanoparticles, such as cell membrane coated nanoparticles, exosomes or microparticles, have displayed good biocompatibility, prolonged circulation, as well as tumor-targeting capacity. Given that the surface protein composition of biomembrane may be crucial for their function, preservation of biomembrane integrity and stability is very important for their application in drug delivery[3]. Here, we develop a biocompatible tumor cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs), which preserve the membrane integrity for excellent tumor targeting ability. Western blot and immunofluorescence results indicate exosomes exits on the surface of DOX@E-PSiNPs. DOX@E-PSiNPs, regardless of origin, exhibit excellent cell uptake and cytotoxicity ability in both cancer cells and cancer stem cells (CSCs). After intravenous injection into H22 tumor-bearing mice, more DOX@E-PSiNPs can accumulate in tumor tissues, especially in tumor cells and side population cells (SPs) with CSCs properties, even better than high dosage of DOX-treated group. DOX@E- PSiNPs are easy to extravasate from the blood vessels and penetrate into deep tumor parenchyma. Tumor volume, weight and survival experiments indicate DOX@E-PSiNPs possess remarkable antitumor effects at relatively lower DOX concentration in subcutaneous, orthotopic and metastatic tumor models. Meanwhile, SPs proportion and formation of tumor spheres in 3D-fibrin gels results reveal DOX@E-PSiNPs can effectively reduce CSCs. Furthermore, cytokine in serum, blood phase analysis, and hematoxylin-eosin (H&E) staining of major organs show extraordinary biocompatibility of DOX@E-PSiNPs. In conclusion, these results prove DOX@E-PSiNPs is an efficient tumor targeting carrier and provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.

References [1] Mitragotri, S., Burke, P. A. & Langer, R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat. Rev. Drug Discov.13(2014), 655–672. [2] Anna Salvati, Andrzej S. Pitek, Marco P. Monopoli, et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat. Nanotechnol. 8(2013), 137–143. [3] M. Frydrychowicz, A. Kolecka‐Bednarczyk, M. Madejczyk, et al. Exosomes–structure, biogenesis and biological role in non-small-cell lung cancer. Scand J. Immunol. 81(2015), 2–10. [4] Su Chul Jang, Oh Youn Kim, Chang Min Yoon, et al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano 7 (2013), 7698–7710.

4th CASNN Annual Meeting 2019

234 Precise targeting of bile acid receptors for liver cancer therapy Wantong Song1,*, Guofeng Ji1, Leaf Huang2 and Xuesi Chen1

1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China. 2Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. E-mail: [email protected]

Liver is the most common site of metastasis in many cancer types, and liver cancer is among the leading cause of cancer-related deaths. Several immune cells were proved important for liver cancer control [1]. Among them, natural killer T (NKT) cells, a subset of lymphocytes abundant in the liver, play an important role in antitumor immunity. NKT cells are recruited to the liver through the interaction between C-X-C Motif Chemokine Receptor 6 (CXCR6) on NKT cells and C-X-C Motif Chemokine Ligand 16 (CXCL16) secreted mainly by the liver sinusoidal endothelial cells (LSECs). In a recent report, gut-derived bile acid was shown to have direct influence on the NKT cells recruitment to the liver. Specially, primary bile acid was proved to promote secretion of CXCL16 by LSECs and enhance NKT-based therapy for liver cancer, while secondary bile acid functioned in the opposite way [2]. Farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1) are the primary receptors for primary and secondary bile acids, respectively. Therefore, we hypothesize that using FXR agonists or GPBAR1 antagonists may help in liver cancer therapy. FXR and GPBAR1 are widely expressed in the gut intestinal system, and systemic usage of agonists or antagonists for FXR or GPBAR1 may result in severe adverse effects. To solve this obstacle, we designed a nanoformulation of obeticholic acid (a clinically approved FXR agonist) for precise targeting the bile acid receptors in the LSECs, leveraging the intrinsic properties of LSECs as the major cells in liver for taking up nanoparticles [3]. In an established orthotopic murine liver cancer model, we showed that the nano- approach resulted in superior effect in stimulating NKT cells for control over liver cancer. The study provides a new paradigm for modulating bile acid related pathway for liver cancer therapy.

References [1] W. Song, K. Tiruthani, Y. Wang, L. Shen, M. Hu, O. Dorosheva, K. Qiu, K.A. Kinghorn, R. Liu, L. Huang, Trapping of Lipopolysaccharide to Promote Immunotherapy against Colorectal Cancer and Attenuate Liver Metastasis, Advanced Materials, 30 (2018) 1805007. [2] C. Ma, M. Han, B. Heinrich, Q. Fu, Q. Zhang, M. Sandhu, D. Agdashian, M. Terabe, J.A. Berzofsky, V. Fako, T. Ritz, T. Longerich, C.M. Theriot, J.A. McCulloch, S. Roy, W. Yuan, V. Thovarai, S.K. Sen, M. Ruchirawat, F. Korangy, X.W. Wang, G. Trinchieri, T.F. Greten, Gut microbiome–mediated bile acid metabolism regulates liver cancer via NKT cells, Science, 360 (2018) eaan5931. [3] H. Zhou, Z. Fan, P.Y. Li, J. Deng, D.C. Arhontoulis, C.Y. Li, W.B. Bowne, H. Cheng, Dense and Dynamic Polyethylene Glycol Shells Cloak Nanoparticles from Uptake by Liver Endothelial Cells for Long Blood Circulation, ACS Nano, 12 (2018) 10130-10141.

4th CASNN Annual Meeting 2019

235 NIR fluorescence guided drug delivery Xiaomin Li

Department of Chemistry & Laboratory of Advanced Materials, Fudan University, Shanghai 200433, P. R. China Email: [email protected]

Imaging-guided drug delivery, so-called “theranostic”, is a concept of integrating imaging and therapy into a single platform for use in the next generation of personalized medicine to meet the challenges in modern health care. The diagnostic role of theranostic agents reports the presence of a disease, its status, and its response to a specific treatment, while the nanocomposites carry chemo-, radio- or gene therapeutics or combinations of these. Here, we present the development and progress of the NIR fluorescence guided drug delivery based on the nanocomposites of NIR fluorescent nanomaterials and mesoporous SiO2 nanoparticles. The NIR fluorescent nanomaterials in the nanocomposites are used as both imaging agents for the tracking of the nanocarriers, monitoring of the drug release and light sources for triggering the drug release or light induced therapy. The successive layer-by-layer coating strategy are developed for the core@shell structure engineering of NIR fluorescent nanomaterials. A series of novel core@shell structures with unique NIR optical properties were fabricated, including core@shell structure with uniform shell, controllable doping positions with multi-color emissions, homogeneous doping enhanced upconversion efficiency, core/multi-shell structure for up/down converting dual-mode bioimaging, filtration shell mediated orthogonal excitations-emissions upconversion luminescence, etc. Then, we combine the obtained versatility NIR fluorescent nanomaterials with mesoporous SiO2 for the NIR fluorescence guided drug delivery. To address the shortcomings confronted by the traditional symmetric spherical based nanocarriers in drug delivery, series of asymmetric nanocarriers were developed based on the novel anisotropic growth strategy, including Janus, single-hole hollow, nano-thermometer, di or tri-block Janus, nanotrucks etc. The obtained nanocomposites possess both unique properties of mesoporous nanomaterials and unique NIR optical properties. Most importantly, the obtained asymmetric nanocomposites possess unique multiple independent surfaces, compositions, functions etc., which are ideally for the co-delivery of multi-guests with quite different properties (hydrophilicity/hydrophobicity, acidity/basicity, sizes etc.).

References [1] T. Zhao, P. Wang, Q. Li, A. A. Al-Khalaf, W. N. Hozzein, F. Zhang, X. Li,* D. Zhao,* Near- infrared triggered decomposition of nanocapsules with high tumor accumulation and stimuli responsive fast elimination, Angew. Chem. Int. Ed. 57 (2018) 2611-2615. [2] L. Liu, S. Wang, B. Zhao, P. Pei, Y. Fan, X. Li,* F. Zhang,* Er3+ sensitized 1530 nm to 1180 nm second near-infrared window upconversion nanocrystals for in vivo biosensing, Angew. Chem. Int. Ed. 57 (2018) 7518-7522. [3] X. Li, Z. Guo, T. Zhao, Y. Lu, L. Zhou, D. Zhao, F. Zhang,* Filtration shell mediated power density independent orthogonal excitations-emissions upconversion luminescence, Angew. Chem. Int. Ed. 55 (2016) 2464-2469. [4] X. Li, F. Zhang,* D. Zhao,* Lab on upconversion nanoparticles: optical properties and applications engineering via designed nanostructure, Chem. Soc. Rev. 44 (2015) 1346-1378. [5] X. Li, L. Zhou, Y. Wei, A. M. El-Toni, F. Zhang,* D. Zhao,* Anisotropic growth-induced synthesis of dual-compartment janus mesoporous silica nanoparticles for bimodal triggered drugs delivery, J. Am. Chem. Soc. 136 (2014) 15086-15092. [6] X. Li, L. Zhou, Y. Wei, A. M. El-Toni, F. Zhang,* D. Zhao,* Anisotropic encapsulation-induced synthesis of asymmetric single-hole mesoporous nanocages, J. Am. Chem. Soc. 137 (2015) 5903-5906.

4th CASNN Annual Meeting 2019

236 Preparation and characterization of quercetin / paclitaxel nanoparticles Xiaoming Cui1,Zhilu xu1, Dejun ding1 ,Xiuwen guan1, Jinlong ma1, Weifen Zhang1,2,3,4*

1Department of pharmaceutics, School of Pharmacy, Weifang Medical University, Weifang 261053, Shandong, P.R. China. E-mail: [email protected] Engineering Research Center for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang 261053, Shandong, P.R. China.3Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang 261053, Shandong, P.R. China. 4Institute for Smart Materials and Regenerative Medicine, Weifang Medical University, Weifang 261053, Shandong, P.R. China. E-mail:[email protected]

Abstract: According to a WHO report, in 2015, about 8.2 million people died from cancer of which 16.7% had lung cancer [1]. Paclitaxel (PTX) is widely used for anticancer, but its therapeutic efficiency is limited by hydrophobicity and severe systemic toxicity[2]. And querecetin (QUE) has been reported as a natural bioflavonoid with great antitumor effect. Chitosan (CTS), cationic natural copolymer, is a good candidate for using in the drug delivery system[3] on account of its good biocompatibility. The purpose of our study was to prepare nanoparticles based on cetuximab (Cet) tagged chitosan (CTS) as tumor targeted delivery system for PTX and QUE (PTX/QUE Cet-CNPs), using the ionic crosslinking technique.Successfully conjugation of cetuximab on the surface of chitosan confirmed by bicinchoninic acid (BCA) assay. The two NPs were co-delivered in a certain ratio to improve the treatment efficiency and minimize the side effect. MTT test conformed that NPS had good cytocompatible. And TEM showed that PTX/QUE Cet-CNPs are spherical and uniform distributed and particles-size analysis displayed a particle size of 271.1 ± 9.1 nm and 278.4 ± 7.6 nm, respectively. Moreover, NPs displayed sustained release profile in PBS (pH 5.5) and could be successful uptaked into lung cancer A549 cells. All the results showed that the QUE/PTX Cet-NPs was sucessfully prepared and could provide a promising vehicle for the treatment of lung cancer.

Fig. 1. Illustration of Cet/QUE/PTX -Chitosan nanopaticles with promising performance. Acknowledgments: The authors are grateful for the generous financial support from National Natural Science Foundation of China (No. 81774125)

References [1] Lee W H, Loo C Y, Traini D, et al. Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges[J]. Asian Journal of Pharmaceutical Sciences, 2015, 10(6):481-489. [2] Xiang J, Wu B, Zhou Z, et al. Synthesis and evaluation of a paclitaxel-binding polymeric micelle for efficient breast cancer therapy[J]. Science China, 2018, 61(4):1-12. [3] Young-Ok Son, Sung-Ho Kook, Ki-Choon Choi, et al. Quercetin, a bioflavonoid, accelerates TNF- α-induced growth inhibition and apoptosis in MC3T3-E1 osteoblastic cells[J]. European Journal of Pharmacology, 2006, 529(1):24-32.

4th CASNN Annual Meeting 2019

237 Intracellular enzyme triggered assembly of amino acids modified gold nanoparticles for accurate cancer therapy with multimode Tao Liu [a], Bolei Cai [b] and Xin Chen*[a]

[a] Department of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Xi’an Jiao Tong University, Institution of Polymer Science in Chemical Engineering, Xi’an 710049, P. R. China [b] State Key Laboratory of Military Stomatology, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi’an 710032, China E-mail: [email protected]

Photothermal therapy (PTT) triggered by near-infrared (NIR) light has attracted great attentions for anti-cancer applications due to its spatiotemporal addressability, minimal invasiveness, and high therapeutic efficiency 1. However, in the conventional studies, photothermal therapeutic agents were all designed as sustained heat sources under irradiation regardless of their location 2, 3, which may cause random damages to normal tissues during therapy meanwhile reduce the efficiency of cancer therapy 4. In situ assembly of biocompatible AuNPs in tumor microenvironment to spontaneously form photothermal agent for selective tumor therapy, may offer a solution to address these issues. Thus it is highly meaningful to develop a strategy for accurately manipulating the assembly of AuNPs in tumor for selective and effective tumor therapy.

This work focuses on developing a multiple amino acid modified gold nanoparticles (AuNPs-Fe- Glu-Lys) with pH switchable zwitterionic surface, enzyme (TGase) responsive photothermal property and H2O2 selective catalytic performance. This design was expected to combine the tumor selectivity, tumor-triggered photothermal therapy and catalytic medicine for efficient and accurate tumor therapy with Multimode. At low pH values around tumor cells, the as-prepared AuNPs-Fe-Glu-Lys would switch from electric neutrality to positive charge, providing efficient cellular uptake only to tumor cells. Then the intracellular TGase started trigger the polymerization, followed with the AuNPs-Fe- Glu-Lys aggregation and enhanced photothermal property. Moreover, the effective Fe2+ delivery of AuNPs-Fe-Glu-Lys results in H2O2-responsive radicals generation through the iron-based Fenton reaction, which further raised the therapeutic efficiency. The all-in-one device performed not only an eightfold cytotoxicity against tumor cells compared with normal cells under 48 h after NIR irradiation, but a complete inhibition and gradual elimination of tumor tissue after three weeks of treatment, illustrating its potential for accurate tumor therapy.

References: [1] Cheng, L.; Wang, C.; Feng, L.; Yang, K.; Liu, Z.: Functional Nanomaterials for Phototherapies of Cancer. Chem. Rev. 2014, 114, 10869-10939. [2] Deng, X.; Li, K.; Cai, X.; Liu, B.; Wei, Y.; Deng, K.; Xie, Z.; Wu, Z.; Ma, P. a.; Hou, Z.; Cheng, Z.; Lin, J.: A Hollow-Structured CuS@Cu2S@Au Nanohybrid: Synergistically Enhanced Photothermal Efficiency and Photoswitchable Targeting Effect for Cancer Theranostics. Adv. Mater. 2017, 29, 1701266. [3] Zhang, P.; Wang, Y.; Lian, J.; Shen, Q.; Wang, C.; Ma, B.; Zhang, Y.; Xu, T.; Li, J.; Shao, Y.; Xu, F.; Zhu, J.-J.: Engineering the Surface of Smart Nanocarriers Using a pH-/Thermal-/GSH-Responsive Polymer Zipper for Precise Tumor Targeting Therapy In Vivo. Adv. Mater. 2017, 29, 1702311. [4] Huo, M.; Wang, L.; Chen, Y.; Shi, J.: Tumor-selective catalytic nanomedicine by nanocatalyst delivery. Nature Communications 2017, 8, 357.

4th CASNN Annual Meeting 2019

238 + Biomimetic hybrid nanozymes with self-supplied H and accelerated O2 generation for enhanced starvation and photodynamic therapy against hypoxic tumors Xue Yang, Ying Yang, Fang Gao, Cheng-Gen Qian, and Min-Jie Sun

Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China Email: [email protected]

Nanozymes, which employ nanomaterials to mimic the functions of natural enzymes with tunable enzymatic activity, and low production cost, which have been considered as the most promising theranostic agents for various diseases treatment including antiaging, stroke and inflammation. However, how to control their enzymatic activities in complicated tumor microenvironment, especially hypoxia and acidic microenvironment, is still challenging. [1] In our research, we report a biomimetic hybrid nanozyme (named rMGB) which integrates natural enzyme glucose oxidase (Gox) with nanozyme manganese dioxide (MnO2). In this work, for the first time, we raised up the new strategy for alleviating tumor hypoxia with achieving self-supplied H+ and accelerating O2 generation and enhanced anticancer efficiency. The rMGB can produce continuous O2 under normoxic condition as well as hypoxia condition. Specifically, MnO2 can react with endogenous

H2O2 to produce O2 for accelerating glucose consumption for tumor starvation therapy. Meanwhile generated gluconic acid will further local accelerate O2 generation via enhancing catalytic efficiency of MnO2 under acidic condition, which could alleviate tumor hypoxia and accelerate the reactive oxygen species (ROS) generation in tumor photodynamic therapy (PDT). The designed biomimetic hybrid nanozyme system exhibited a powerful synergistic therapeutic effect of starvation therapy and PDT particularly in hypoxic tumors, which had been effectively demonstrated enhanced antitumor effects in vitro and in vivo. In addition, the rMGB was a safe drug delivery system that did not cause any systemic effects due to RBCs membrane’s long-circulating ability and highly biological safety. This hybrid nanozyme would further promote the development of biomimetic nanozyme for more effective cancer treatment in spite of the hypoxic tumors.

Figure 1. (A) Schematic design of the biomimetic hybrid nanozyme (rMGB) which achieving self- + supplied H and accelerating O2 generation for alleviating tumor hypoxia (B) The scheme of two fishs help each other when both are in humble circumstances (MnO2 with GOx)

References : [1] M. Huo, L. Wang, Y. Chen, J. Shi, Tumor-selective catalytic nanomedicine by nanocatalyst delivery, Nature communications, 8 (2017) 357.

4th CASNN Annual Meeting 2019

239 Covalent assembly of small biomolecules for tumor imaging and therapy Yamei Liu, Xuehai Yan*

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China *E-mail: [email protected] Covalent assembly based on small biomolecules plays a critical role in constructing nanostructures in nanomedicine. In this presentation, we report a covalent assembly strategy via the reaction between amine-containing peptides and crosslinking agents for fabricating nanodrugs towards tumor imaging and therapy. The resulting nanodrugs have high stability in complex physiological environments, controllable degradation rates, adjustable fluorescence emission and/or enhanced photothermal effect. Firstly, we fabricated stable and degradable nanocarriers capable of loading indocyanine green by covalent assembly between genipin and a functional bola-amino acid with enhanced photothermal effect. The nanocarriers are responsive to glutathione because the bola-amino acid contains disulfide bonds. Intriguingly, nanoparticles with controllable fluorescence emission and photothermal effect can be selectively produced by manipulating the kinetically process (the covalent reaction time and temperature) between peptides and the crosslinking agents. The fluorescent nanoparticles show adjustable fluorescence emission from blue to red luminescence and thus can be applied for tumor imaging. The photothermal nanoparticles show a large photothermal efficiency under near-infrared (NIR) light and thus can be applied for photoacoustic imaging guided photothermal therapy. Hence, our results demonstrate that covalent assembly of small biomolecules is a versatile strategy for design of supramolecular nanodrugs towards multiple biomedical applications.

Figure 1. Covalent assembly based on small biomolecules for the design of robust nanodrugs with controllable degradation rate, adjustable fluorescence emission and photothermal effect.

References [1] Y. Liu, L. Zhao, R. Xing, T. Jiao, W. Song, X. Yan*, Covalent assembly of amphiphilic bola- amino acids into robust and biodegradable nanoparticles for in vitro photothermal therapy, Chem. Asian J. 13 (2018) 3526-3532. [2] S. Li, Y. Liu, R. Xing, X. H. Yan*, Covalent assembled dipeptide nanoparticles with adjustable fluorescence emission for multi-color bio-imaging, ChemBioChem 20 (2019) 555-560. [3] L. Zhao, Y. Liu, R. Chang, R. Xing, X. Yan*, Supramolecular photothermal nanomaterials as an emerging paradigm toward precision cancer therapy, Adv. Funct. Mater. 29 (2019) 1806877. [4] Q. Zou, M. Abbas, L. Zhao, S. Li, G. Shen, X. Yan*, Biological photothermal nanodots based on self-assembly of peptide−porphyrin conjugates for antitumor therapy, J. Am. Chem. Soc. 139 (2017) 1921-1927. [5] M. Abbas, Q. Zou, S. Li, X. Yan*, Self-Assembled Peptide- and Protein-Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy, Adv. Mater. 29 (2017) 1605021.

4th CASNN Annual Meeting 2019

240 Cell membrane-cloaked oil nanosponges enable dual-modal detoxification Yijie Chen1,2, Yue Zhang1, Jia Zhuang1, Joo Hee Lee1, Licheng Wang1, Ronnie H. Fang1, Weiwei Gao1, Liangfang Zhang1

1Department of Nanoengineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA 2Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, China Email: [email protected]

The harmful biological or chemical agents have emerged as a major threat to global health, and thus technologies for effective detoxification are in great need. Cell membrane coating strategy has been widely used in nanotechnology to provide artificial materials with cell-like functions, such as red blood cell membrane-coated nanoparticles were able to neutralize broad-spectrum of pore-forming toxins[1] or to suppress the lethality of whole secreted toxins from ‘superbug’ bacteria[2]. Despite the remarkable applications, the membrane-only working mechanism may limit the overall detoxification capacity. Herein, to improve the detoxification ability, we develop a unique ‘core-shell’ oil nanosponge (Oil-NS) that exert dual-modal detoxification function (Scheme below). The Oil-NS with superior colloidal stability was synthesized by wrapping the red blood cell membrane onto oil nanodroplets, in which the oil core can non-specifically sock up toxicants through physical partition effect and the cell membrane shell can specifically neutralize toxicants through biological binding receptors. To test Oil-NS for dual-modal detoxification, three organophosphates (OPs) include paraoxon, diisopropyl fluorophosphate, and dichlorvos were introduced. As a result, Oil-NS not only captured the OPs effectively but also protected the AChE activity on RBCs from OPs attacking. In mouse models of OP poisoning, the Oil-NS reduced clinical signs of OP intoxication, maintained the AChE activity on RBCs, and greatly improved mouse survival in both therapeutic regimen and prophylactic regimen. Overall, Oil-NS combines the merits of both cell membrane and oil nanodroplets for safe and effective detoxification, which also serve as a prototype of multimodal detoxification platforms.

References [1] Y. Chen, M. Chen, Y. Zhang, J.H. Lee, T. Escajadillo, H. Gong, R.H. Fang, W. Gao, V. Nizet, L. Zhang, Broad-Spectrum Neutralization of Pore-Forming Toxins with Human Erythrocyte Membrane- Coated Nanosponges., Adv. Healthc. Mater. (2018). [2] Y. Chen, Y. Zhang, M. Chen, J. Zhuang, R.H. Fang, W. Gao, L. Zhang, Biomimetic Nanosponges Suppress In Vivo Lethality Induced by the Whole Secreted Proteins of Pathogenic Bacteria., Small. 15 (2019) e1804994.

4th CASNN Annual Meeting 2019

241 Co-delivery of anti-PD-L1 siRNA and CpG with roller microneedle electrode array (RMEA) for cancer immunotherapy Tongren Yang1, Dong Huang2 Chunhui Li,1 Zhihong Li2, Yuanyu Huang1, *

1 School of Life Science, Beijing Institute of Technology, Beijing 100081, China 2 Institute of Microelectronics, Peking University, Beijing 100871, China Corresponding authors: [email protected] (Y. Huang) Introduction: How to deliver small interfering RNA (siRNA), a promising therapeutic modality that is used to treat various diseases, to the desired tissues safely and efficiently is the key scientific issue for drug development[1]. Electroporation is a powerful physical delivery technology, especially for those hard-to-transfect cells and local tissues. How to achieve high efficiency, nondestructive electroporation of nuclei acids at low voltage constitute the main challenge in the field [2]. In this study, electroporation with novel Roller Microneedle Electrode Array (RMEA) was proposed to deliver anti- PD-L1 siRNA and CpG2395 to local tumors, and the performances of cancer immunotherapy were thoroughly investigated. Methods: Confocal observation, histopathology assay, tumor growth recording, in vivo imaging, and FACS, etc., were utilized to evaluate the delivery and treatment efficiency. siRNAs were provided by Suzhou Ribo Life Science, Ltd., and RMEA was prepared by Peking University. Results: It was demonstrated that the RMEA can generate uniform electric field under electric pulse stimulation. siRNAs were successfully delivered to mouse legs at low voltage, and stayed for more than five days with one time of operation. In CT26 murine tumor model, co-delivery of anti-PD-L1 siRNA and CpG2395 with RMEA significantly inhibited tumor growth, enhanced the survival rate, and elevated the CD4 and CD8 positive T cell populations.

Figure 1. Co-delivery of siRNA and CpG2395 for cancer immunotherapy. (a-c) Schemes of proposed RMEA; (d and e) Electric field generated by RMEA; (f and g) In vivo imaging (f) and cryosection observation (g) of Cy5-siRNA-electroporated mouse legs; (h and i) Enhanced survival rat (h) and tumor growth inhibition (i) with proposed treatment strategy. Conclusion: Efficient delivery of siRNA and CpG oligo to local tissue and ideal immunotherapeutic effect were successfully achieved by proposed RMEA, which constitute a novel biomolecule delivery and disease treatment platform. Keywords: siRNA, In vivo electroporation, CpG, Cancer Immunotherapy

Reference: [1] Y. Weng, H. Xiao, J. Zhang, X.J. Liang, Y. Huang, RNAi therapeutic and its innovative biotechnological evolution, Biotechnol Adv, (2019) doi: 10.1016/j.biotechadv.2019.1004.1012. [2] D. Huang, D. Zhao, X. Wang, C. Li, T. Yang, L. Du, Z. Wei, Q. Cheng, H. Cao, Z. Liang, Y. Huang, Z. Li, Efficient delivery of nucleic acid molecules into skin by combined use of microneedle roller and flexible interdigitated electroporation array, Theranostics, 8 (2018) 2361-2376.

4th CASNN Annual Meeting 2019

242 Harnessing the softness: pickering emulsion for enhanced prophylactic and therapeutic vaccinations Yufei Xia1, Guanghui Ma*, Jie Wu, 1 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China E-mail: [email protected]

There is an urgent need to develop potent adjuvant for both humoral and cellular responses. Bionic design is regarded as the golden rule to develop successful adjuvant platforms for prophylactic and therapeutic vaccinations. Previous attempts have focused on mimic the sizes, shapes, charges and compositions of pathogens the sizes, shapes, charges and compositions of pathogens. However, membrane dynamic curvature and lateral diffusion of endocytosis targets have long been neglected, which might alternatively confer effective strategy to elicit robust prophylactic and therapeutic immune responses. To address this, we developed intelligent Pickering emulsion, where PLGA nanoparticles stabilized squalene (PPAS) instead of surfactant, to function as an elastic and biodegradable adjuvant, which increased antigen loading efficiency. This Pickering emulsion was unraveled with increased pliability and lateral mobility, compared with surfactant stabilized emulsion or solid micro-, nanoparticles. In addition, the force-dependent deformation and dynamic fluidity of PPAS stimulated the multivalent three-dimensional interactions with antigen-presenting cells. By contrasting with the clinical-relevant adjuvants, including alum, MF59, and AS04, the developed droplets exerted potent immune protections against influenza virus challenge and enhanced efficiency in both E.G7/OVA and B16/MUC1 anti-tumor therapies. This work offered a promising alternative strategy, which exploited the force-dependent deformation and lateral mobility of particulate adjuvants for robust vaccinations.

Figure 1. Schematic illustration on the softness effect

Reference: [1] Xia, YF, Ma GH et al, Exploiting the Pliability and Lateral Mobility of Pickering Emulsion for Enhanced Vaccination, Nature Mater., 2018, 17: 187-194. [2] Xia YF, Wu J, Su ZG, Ma GH, et al. Bridging the Systemic and Gastrointestinal Immune Responses via Oil-in-polymer Capsules, Adv. Mater., 2018, 30, 1801067 (inside cover). [3] Xia YF, Na XM, WU J, MA GH*, The horizon of emulsion particulate strategy: Engineering hollow particles for biomedical applications. Adv. Mater., 2018, 1801159.

4th CASNN Annual Meeting 2019

243 In vivo multimodal imaging and enhanced cancer radiotherapy by hemoglobin-encapsulated gadolinium based coordination nanoparticles Yunlu Dai*

Faculty of Health Sciences, University of Macau, Macau SAR 999078, China, *Email: [email protected]

Introduction Radiotherapy is a quite common method for cancer treatment by exploiting the oxygen-centered radicals generation for DNA damage by oxygen and water in tumor site. However, the efficacy is not high because the hypoxic tumor microenvironment [1]. Therefore, it is still a big challenge to deliver oxygen to tumor and enhance the radiotherapy efficacy. The high Z metals could enhance the treatment of radiotherapy. The polyphenols could chelate with various metals for biomedical applications [2].

Methods We designed and prepared a gadolinium (Gd) based coordination nanoparticles by encapsulating haemoglobin (Hb) in the core of nanoparticles. The Hb can be used as the oxygen carrier to reduce the hypoxic environment in the tumor and enhance the radiotherapy efficacy. The Gd can chelate with PEG-polyphenols to coat on the surface of Hb by electrostatic interaction [3]. The free Gd and PEG- polyphenols can be washed by PBS.

Results The monodispersed nanoparticles with size around 40 nm were synthesized successfully. The nanoparticles are stable in PBS. The nanoparticles could absorb oxygen by Hb. Moreover, the as- prepared nanoparticles could enhance the photoacoustic imaging in vivo as the nanoparticles could delivery oxygen to the tumor. The nanoparticles are good candidates as contrast agents for T1 magnetic resonance imaging [3]. The high-Z metal Gd could also enhance the radiotherapy efficacy.

Conclusion In this research, we have designed and prepared the Gd based coordination nanoparticles by encapsulating Hb in the core. The nanoparticles could delivery oxygen to the tumor side by EPR effect and overcome the tumor hypoxia. The tumor accumulation of nanoparticles was investigated by photoacoustic imaging and magnetic resonance imaging. Furthermore, the nanoparticles could inhibit the tumor growth, promote the cancer radiotherapy efficacy, and reduce the side effect.

References [1] X. Chen, J. Song, X. Chen, H. Yang. X-ray-activated nanosystems for theranostic applications, Chem. Soc. Rev. 48 (2019) 3073–3101. [2] H. Ejima, J. Richardson, K. Liang, J. Best, M. Koeverden, G. Such, J. Cui, F. Caruso. One-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering, Science, 341 (2013) 154–157. [3] Y. Dai, Z. Yang, S. Cheng, Z. Wang, R. Zhang, G. Zhu, Z. Wang, B. Yung, R. Tian, O. Jacobson, C. Xu, Q. Ni, J. Song, X. Sun, G. Niu, X. Chen. Toxic reactive oxygen species enhanced synergistic combination therapy by self-assembled metal-phenolic network nanoparticles. Adv. Mater. 30 (2018) 1704877.

4th CASNN Annual Meeting 2019

244 Size switchable nanoclusters fueled by extracellular ATP for promoting the deep penetration and MRI guided tumor photothermal therapy Zhanwei Zhou, Ruoxi Yang, Hui Wu, Alan Xu, Minjie Sun

Department of Pharmaceutics, China Pharmaceutical University,24 Tong Jia Xiang, Nanjing 210009, China Email: [email protected]

Proteins based theranostic agents (PBTA) exhibited superior performance on the diagnosis and therapy of cancers.[1] However, the in vivo applications of PBTA are largely limited by the undesired accumulation, penetration or selectivity.[2] Here, an ATP-supersensitive protein cluster is fabricated for promoting the PBTA delivery and enhancing the MRI guided tumor photothermal therapy. Gd3+ and CuS coloaded small BSA nanoparticles (GdCuB) are synthesized as the model protein with a size of 9 nm and are encapsulated into charge switchable polycations (DEP) to form DEP/GdCuB nanoclusters of 120 nm. In blood circulation, the relative larger size of DEP/GdCuB significantly extends the half- life time of GdCuB and enhances the tumor accumulation of theranostic agent. When the DEP/GdCuB clusters reach tumor site, the extracellular ATP of 0.1-0.4 mM[3] could effectively trigger the release of small-sized GdCuB, resulting in the tumoral deep penetration as well as the activation of T1-weighted −1 −1 MRI (r1 value switched from 2.8 to 11.8 mM ·s ). Furthermore, this delivery strategy also improves the tumoral photothermal therapy efficacy after the irradiation of 1064 nm laser with the MRI guided (Scheme 1). Our study of ATP-activated nanocluster develops a novel strategy for tumor deep penetration and on/off imaging of PBTA by size switchable technology and reveals the potential for MRI guided therapy of cancers.

Scheme 1. Schematic illustration of the assembly/disassembly of extracellular ATP-activated DEP/GdCuB clusters for deep penetration and amplifying MRI guided tumor photothermal therapy.

References [1] Q. Chen, Z. Liu, Albumin carriers for cancer theranostics: a conventional platform with new promise, Adv. Mater. 28(47) (2016) 10557-10566. [2] Y. Lu, W. Sun, Z. Gu, Stimuli-responsive nanomaterials for therapeutic protein delivery, J. Controlled Release 194 (2014) 1-19. [3] J. Gao, J. Li, W.-C. Geng, F.-Y. Chen, X. Duan, Z. Zheng, D. Ding, D.-S. Guo, Biomarker Displacement Activation: a General Host-Guest Strategy for Targeted Phototheranostics in Vivo, J. Am. Chem. Soc. 140(14) (2018) 4945-4953.

4th CASNN Annual Meeting 2019

245 Hyaluronan coated peptide nanoparticle clusters with size and charge transformability in tumor microenvironment Zhaoqing Cong 1, 2, Lu Zhang 2, Siqi Ma 1, Kit S. Lam 2, Feifei Yang 1*, Yonghong Liao 1*

1 Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, 151 Malianwa North Road, Haidian District, Beijing 100193, China 2 Department of Biochemistry and Molecular Medicine, UC Davis NCI-designated Comprehensive Cancer Center, University of California Davis, Sacramento, California 95817, United States E-mail: [email protected] (Z. Cong); [email protected] (F.Yang); [email protected] (Y. Liao) Effective cancer nanotheranostics are subjected to various challenges such as undesirable blood circulation time, premature drug release in the circulation, insufficient tumor accumulation, limited tumor tissue penetration and inadequate drug release in the targeted cell/tissue. To this end, multistage delivery systems with size-switching ability have been utilized to circumvent these obstacles[1]. However, these size-switching strategies were mainly designed for mono-therapy, lacking of diagnostic and combined therapeutic functions[2]. Herein, we reported a size- and charge-transformable nanoplatform sensitive to the tumor microenvironment (TME). Such a delivery system enables to integrate different anticancer modalities, such as chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT), to achieve a high antitumor efficacy. In this study, an amphiphilic hexadecapeptide derivative, which consisted of an antifouling and hydrophilic EK4 chain decorated with phenyl boronic acid (PBA) and dendritic polylysine segment modified with cholic acids (CA) and indocyanine green derivative (ICGD), was synthesized by solid-phase synthesis and this polypeptide was able to self-assemble into slightly positively charged ultra-small micelles (< 30 nm) with the CMC value being ~ 0.04 μM. After the addition of dopamine decorated hyaluronic acid (HA), micelles were stacked into large and negatively charged HA coated nanoparticles (~ 130 nm) through the formation of boronate between PBA and dopamine. The latter nanoparticles exhibited decreased drug release rate and were sensitive to low pH and hyaluronidase conditions in the TME to discharge the positively charged ultra-small micelles, accelerating the drug release. The present dual transformable nanoplatform combining chemotherapy with photothermal and photodynamic therapy are expected to improve targeted tumor treatment.

Fig. 1. Schematic illustration of the preparation of HA-K2 NPs and the TME sensitive size- and charge-transformability. Acknowledgements: This work was supported by the Ministry of Science and Technology of the People’s Republic of China [2018FY100703]; CAMS Initiative for Innovative Medicine [2017-I2M-1- 013] and program of China Scholarship Council (CSC) (No. 201706210390).

References [1] J. Chen, J. Ding, Y. Wang, J. Cheng, S. Ji, X. Zhuang, X. Chen, Sequentially responsive shell‐stacked nanoparticles for deep penetration into solid tumors, Advanced Materials, 29 (2017) 1701170. [2] X. Xue, Y. Huang, R. Bo, B. Jia, H. Wu, Y. Yuan, Z. Wang, Z. Ma, D. Jing, X. Xu, W. Yu, T.Y. Lin, Y. Li, Trojan Horse nanotheranostics with dual transformability and multifunctionality for highly effective cancer treatment, Nat Commun, 9 (2018) 3653.

4th CASNN Annual Meeting 2019

246 Bioinspired Peptide Assemblies with Tunable Optical Properties Zhen Fan

School of Material Science and Engineering, Tongji University, Shanghai, 201804, China Email: [email protected]

Due to intrinsic limitations of low biocompatibility and challenging modulation, the utilization of conventional inorganic quantum confined photoluminescent materials in bio-imaging and bio-machine interface faces critical restrictions. Meanwhile, peptide nanostructures are biodegradable and are suitable for many biomedical applications. However, to be useful imaging probes, the limited intrinsic optical properties of peptides must be overcome.

This speech present peptides serve as building blocks to further self-assemble into quantum confined supramolecular structures with diverse morphologies and photoluminescence properties. Especially, the emission can be tuned from the visible to the near-infrared region (420 nm to 820 nm) by modulating the amino acid sequence and self-assembly process, which allows the peptide assemblies to act as imaging and sensing probes. No obvious cytotoxic effect is observed for these peptide assemblies, and their utilizations for in vivo imaging and as phosphors for light-emitting diodes is demonstrated. In addition, after modification with cancer targeting peptide moieties, fluorescent peptide assemblies could combine the targeted imaging and drug delivering for cancer theranostics. Moreover, the drug delivery to tumor sites and therapeutic responses could be monitored with near-infrared fluorescence from peptide assemblies, which may lead to novel potential approaches for bioorganic fluorescence based delivering, imaging and drug release tracking. In summary, the morphologies and optical properties of the peptide assemblies can be tuned, making them potential candidates for supramolecular quantum confined materials providing biocompatible alternatives for broad biomedical and optoelectric applications.

4th CASNN Annual Meeting 2019

247 Tumor acidity and oxidation-responsive block copolymer prodrug filomicelles for nanoparticle shape-boosted drug delivery efficacy Wendong Ke, Zhishen Ge*

CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, China. Email: [email protected] Nanoparticle shapes play an important role in overcoming the drug delivery obstacles during the delivery journey [1]. Among them, filomicelles were demonstrated to circulate for a significantly longer time as compared with the corresponding spherical micelles [2]. Filomicelles can accumulate in tumor tissue and penetrate into deeper tumor tissues, and be internalized by cells more efficiently. These properties endowed them highly promising for in vivo drug delivery. However, up to now, fiber-like block copolymer prodrug (BCP) nanoparticles have never been explored for in vivo anticancer drug delivery. In this report, we prepared three kinds of typical nanoparticles with a comparable cross section diameter (~ 40 nm), including long filomicelles (LFMs) with the length of ~ 2.5 µm, short filomicelles (SFMs) with the length of ~ 200 nm, and spherical micelles (SMs) with a diameter of ~ 40 nm, which were self-assembled from the pH and oxidation dual-responsive block copolymer prodrug, PEG-b- P(CPTM-co-PEMA), consisting of poly(ethylene glycol) (PEG) and copolymerized segments of thioketal-linked camptothecin (CPT) methacrylate monomer (CPTM) and 2- (pentamethyleneimino)ethyl methacrylate (PEMA) (Fig. 1). After intravenous injection, SFMs showed similar blood circulation compared to that of SMs, deepest tumor penetration and best antitumor efficacy. LFMs showed worst in vitro and in vivo performance due to too large size. After tumor accumulation, at tumor pH 6.5, the micelles were positively charged due to protonation of PPEMA moieties. SFMs are demonstrated to be internalized into cells most efficiently due to larger interaction areas than SMs. The thioketal bonds can be cleaved in the intracellular reductive medium to release active CPT drugs. SFMs were demonstrated to suppress tumor growth most efficiently. Therefore, the nanoparticle shape-boosted drug delivery is demonstrated and SFMs showed great potentials to overcome the sequential physiological barriers. This is the first example related to BCP-based filomicelles as drug nanocarriers with proper length, which may pave the way for the design through optimized nanoparticle shapes to improve the delivery efficiency.

LFMs SFMs SMs Fig. 1. The filomicelles self-assembled from the tumor acidity and oxidation-responsive block copolymer prodrugs (BCP). TEM images showed the morphologies of the filomicelles with different lengths.

References [1] S. Venkataraman, J.L. Hedrick, Z.Y. Ong, C. Yang, P.L.R. Ee, P.T. Hammond, Y.Y. Yang, The effects of polymeric nanostructure shape on drug delivery, Adv. Drug Delivery Rev. 63 (2011) 1228- 1246. [2] N.P. Truong, J.F. Quinn, M.R. Whittaker, T.P. Davis, Polymeric filomicelles and nanoworms: two decades of synthesis and application, Polym. Chem. 7 (2016) 4295-4312. 4th CASNN Annual Meeting 2019

248 Herceptin-conjugated paclitaxel loaded PCL-PEG worm-like nanocrystal micelles for the combinatorial treatment of HER2-positive breast cancer Jiahui Peng, Juan Chen, Yuhong Xu, Zixiu Du＊

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China *E-mail: [email protected]

Introduction: We have constructed Herceptin-conjugated, paclitaxel (PTX) loaded, PCL-PEG worm- like nanocrystal micelles (PTX@PCL-PEG-Herceptin) for the combinatorial therapy of HER2- positive breast cancer that exploit the specific targeting of Herceptin to HER2-positive breast cancer cells.

Method: Firstly, amphiphilic PCL2000-MPEG2000 and PCL5000-PEG2000-CHO were selected as the optimized matrix to wrap PTX that self-assembled into worm-like micelles [1] with internal nanocrystal structures (PTX@PCL-PEG) compared to the spherical morphology of blank micelles (Blank-micelles)

(Figure 1). Then the primary amines of Herceptin and aldehydes of PCL5000-PEG2000-CHO exposed on the outside surface of the PTX@PCL-PEG micelles were utilized for the first time to form stable, carbon-nitrogen single linkers (–C–N–) between the antibodies and nanoparticles (PTX@PCL-PEG- Herceptin). Results and conclusions: The present study shows that PTX@PCL-PEG-Herceptin remained relatively stable in the circulation and in the tumor microenvironment, and rapidly targeted and entered into the HER2-overexpressing tumor cells while sparing normal tissues from the toxic effects. PTX@PCL-PEG-Herceptin shrank the tumors and prolonged survival time in a SKBR-3-tumor- xenograft, nude mice model more effectively than TAXOL® and PTX@PCL-PEG. Mechanistic studies showed that PTX@PCL-PEG-Herceptin entered the HER2-positive tumor cells through the caveolin-mediated pathway [2]. The conjugated Herceptin greatly enhanced the binding ability of the nanoparticle conjugate to the targeted SKBR-3 cells. This novel strategy provides a rational and simple antibody-conjugated-nanoparticle platform for the clinical application of combinatorial anticancer treatment.

References [1] X Xin, X Pei, X Yang, Y Lv, L Zhang, W He, et al., Rod-Shaped Active Drug Particles Enable Efficient and Safe Gene Delivery. Adv Sci (Weinh). 4 (2017) 1700324. [2] SM Loverde, ML Klein, DE Discher. Nanoparticle shape improves delivery: rational coarse grain molecular dynamics (rCG-MD) of taxol in worm-like PEG-PCL micelles. Adv Mater; 24 (2012) 3823- 30.

4th CASNN Annual Meeting 2019

249 POSTER PRESENTATIONS CASNN 2019

1. Theranostic metalloporphyrins as sonosensitizers for noninvasive sonodynamic therapy Aiqing Ma, Huaqing Chen, Yingmei Luo, Jiehua Xing, Ruijing Liang, Ting Yin, Mingbin Zheng, Lintao Cai

2. Graphite carbon nitride nanosheets-doped collagen-alginate hydrogel with visible-light driven photocatalytic antibacterial activity for skin defect therapy Huijie Zhang, Baoting Ye, Jinghua Chen

3. MoS2-Fe(III)-DOX nanoplatforms for combined ferroptosis, photothermal and chemotherapy Binbin Ding, Ping’an Ma, Jun Lin

4. A new dendritic contrast agent with intrinsic Mn(II)-based chelators for MRI of cancer micrometastases Bing xiao, Hongxia Xu, Zhuxian Zhou, Xiangrui Liu, Jianbin Tang, Youqing Shen

5. Smart Ce6 containing hollow nanoparticles for enhanced photodynamic therapy Xuemei Wang, Xiaoming Zhang, Chuangkui Kang, Hailin Cong, Bing Yu

6. TiO2nanoparticles functionalized with an AIE luminogen Bingzhao Wu, Hao Ouyang, Huigang Wang

7. Mri-visible and near-infrared emitting molecular probes across blood-brain barrier for phototheranostics application of glioblastoma Bo Li, Hong Xiao, Xintao Shuai

8. NIR-responsive polyprodrug nanoparticles for synergistic cancer combination therapy Changming Dong, Chang Du, Yue Ding

9. Nanocytometry guided characterization and innovation of ros-responsive liposomes Chaoxiang Chen, Kaimin Gao, Hong Lian, Chen Chen, Xiaomei Yan

10. Colloidal hydroxyethyl starch for anti-tumor drugs conjugation Chen Xiao, Xiangliang Yang, Zifu Li

11. Porphyrin-functionized chitosan can self-assemble into micropheres for paclitaxel in vitro release Shu Jiang, Caiwan Ma, Kangrui Wang, Ying Fang, Chenghong Huang

12. A Targeting Nanotherapy containing anti-miR-33 for atherosclerosis regression via cholesterol efflux Chenwen Li, Jianxiang Zhang

13. Targeted photothermal therapy on rabbit with orthotopic breast tumor: Realized by macrophage loaded tungsten carbide Yan Gao, Chunyu Yang, Chongshen Guo

14. Porphyrin loaded porous Au@Pd Nanozyme with photo-enhanced catalytic activity and photodynamic effect for cancer combination therapy

250 Chuan Chen, Gang Liu

15. Facilely synthesized manganese dioxide nanoparticles for MRI-guided photothermal therapy Dan Tian, Hongxia Xu, Bing Xiao, Xiaoxuan zhou, Jianbin Tang, Youqing Shen

16. The effect of fluorine substituents on nir-ii fluorescence properties of dithieno[3,2-b:2′,3′- d]silole-based polymers Tao Li, Bing Liu, Xiaotong Hao, Hancheng Yang, Chuantao Gu

17. Liposomal encapsulation of a hydrophobic fluorophore in hydrophilic interior enhances fluorescence quenching and cellular uptake Chunzhong Xu, Chenhui Cui, Yuqiong Xia, Xianghan Zhang

18. Artificial engineered natural killer cells combined with anti-heat endurance as powerful adjuvant for immuno-enhancing photothermal therapy efficiency of solid tumors Da Zhang, Xiaolong Liu, Jingfeng Liu

19. MGO:Yb@mSiO2 persistent luminescence nanoparticles for NIR-I and NIR-II imaging- guided chemotherapy Dandan Ding, Hongmin Chen

20. Sequentially self-assembled charge-reversal and mitochondrial targeted polysaccharide-based nanoparticles for tumor-targeted drug delivery Lei Fang, Ziting Cheng, Xiaoya Hou, Daquan Chen

21. Dendronized glycopolymer vesicles with prolonged blood circulation and enhanced tumor growth inhibition in photodynamic therapy Dayi Pan, Xiuli Zheng, Kui Luo

22. Electrospun nanofibers cotaining curcumin, β-cyclodextrin decorated silver nanoparticles and chitosan for enhanced wound healing Ni Cheng, Yajing Ji, Wen-tong Li, Dejun Ding

23. Therapeutic effect and synergistic mechanism of coagulation fusion protein/nanogel in the treatment of Hepatocellular carcinoma Dingwen Shi, Ling Li, Yanbing Zhao, Xiangliang Yang

24. Cellular uptake behavior of drug-loaded microparticles prepared by electroporation Dongdong Wang, Xiaoyu Feng, Jun Hu, Xiangliang Yang

25. A novel FePt/MoS2 nanocomposites for potential cancer therapy combining ferroptosis and photothermal Dongsheng Zhang, XiuxiuYao, Yanfei Meng, Xiuwen Zheng

26. Highly toxic reactive oxygen species by iron oxide nanocarrier for efficient codelivery of cantharidin and platinum drug (IV) prodrug Fan Jiang, Binbin Ding, Ping’an Ma, Jun Lin

27. Construction of an enzyme-responsive molecular-biomimetic carrier for tumor targeting and cancer therapy Fangyuan Guo, Qiafan Fu, Chenghao Jin, Xugang Ji, Nan Yu, Gensheng Yang

251 28. pH-selective photodynamic therapy using upconversion nanoparticle based nanoassemblies in deep-seated tumor Fangyuan Li, Yang Du, Daishun Ling

29. Immunostimulatory nanogels to eradicate bladder cancer Faping Li, Bin Liu, Yuxuan Yang, Honglan Zhou

30. Anti-angiogenic activity of bevacizumab-bearing dexamethasone-loaded PLGA nanoparticles Jiaxin Liu, Ge Li, Fei Xu, Fengying Sun, Youxin Li, Lifu Luo

31. A versatile strategy for development of nano-patterned bio-interface array with surface plasomn enhanced YuanYuan Zhang, Ziye Yin, Fuwei Pi

32. A nanoparticle-enhanced brain stimulation technology for stroke rehabilitation Jun Wang, Ye Hong, Rongrong Li, Zixing Xu, Gelin Xu, Gang Ruan

33. A keratin-based injectable hydrogel for wound healing Ying Li, Guang Yang

34. Multi-channel optical imaging for in vivo tracking the fate of transplanted stem cells Guangcun Chen, Dehua Huang, Yejun Zhang, Chunyan Li, Qiangbin Wang

35. Near-infrared fluorescence imaging for vascular visualization in petals of rose Guanjun Deng , Ping Gong, Lintao Cai

36. Virus-mimetic fusogenic polymer for enhanced gene transfection by direct ejecting free DNA to cytoplasma Guowei Wang, Siqin Chen, Zhuxian Zhou and Youqing Shen

37. D-A conjugated polymers for fluorescence and photoacoustic accurate imaging Yawei Miao, Yaowei Zhu, Wentao Zhou, Bing Yu, Hailin Cong

38. Study on in situ activation of anti-tumor immunity by macrophage-loaded poly I:C nanoparticles Haimei Zhou, Lanlan Liu, Huamei He and Lintao Cai

39. pH-sensitive gemcitabine-polyketal conjugated nanoparticles for treating ovarian cancer Haiping Zhong, Jingqing Mu, Yang Xu, Zunkai Xu, Na Yu, Shutao Guo

40. Contrast-enhanced-mri for the diagnosis and monitor of glioma Haiyan Gao, Lijuan Chen, Yan Bai and Meiyun Wang

41. Au@silk fibroin nanoparticles as surface enhanced Raman scattering for probing and imaging of live cells Han Xu, Huigang Wang

42. Flash self-assembly for lipid coating of msn and nanotherapeutics Kam Leon, Hanze Hu

43. Injectable Pd(ii) induced coordination nanogels for overcoming cisplatin-resistance via long- term retention and cancer stem cells killing

252 Hao Zhao, Jiabao Xu, Yanbing Zhao, Xiangliang Yang

44. Autophagy targeting nano-prodrugs for synergistic therapy of metastatic cancer Huifang Wang, Xiangrui Liu, Youqing Shen

45. Protein-templated inorganic hybrid nanocystals for imaging guided phototherapy Ting Li, Tao Yang, Huabing Chen, Hengte Ke

46. Nanomedicine-embedded hydrogel improves chemotherapy of bladder cancer Heping Qiu, Hui Guo, Jianhua Liu, Xiangru Feng, Yuchuan Hou, Jianxun Ding

47. Amino acid metabolic bioorthogonal labeling for dynamical visualizing non-enveloped enterovirus 71 invasion Hong Pan, Fangfang Wang, Xiangjie Yao, Yingmei Luo, Yifan Ma and Lintao Cai

48. Hypoxia targeted photodynamic therapy based on nanophotosensitizers with self-supplied oxygen Hongshang Peng, Jiantao Ping, Lanying Guo

49. Tumor microenvironment responsive nanoparticle for targeted oxygen-elevated phototherapy and ehhanced anti-cancer immunity via immunogenic cancer cell death Huamei He, Lanlan Liu, Ruijing Liang, Haimei Zhou and Lintao Cai

50. An alkaline phosphatase responsive polycationic gene delivery system Huapan Fang, Jie Chen, Lin Lin, Huayu Tian, Xuesi Chen

51. 550℃-stable hollow carbon nitride nanospheres assembled with functional motifs for targeted theranostics Huayi Peng, Ruizhi Xie, Jianhua Xu, Lee Jia

52. Dual-targeted bilayer nanoplatform overcomes fibroblast-rich peritumoural barrier to improve intravesical chemotherapy for bladder cancer Hui Guo, Heping Qiu, Jianhua Liu, Yuchuan Hou, Chunxi Wang, Jianxun Ding

53. Glycogen as efficient carrier for enhancing the immunostimulatory and antitumor effect of CpG oligodeoxynucleotides Huijie Zhang, Li Lai, Jinghua Chen

54. Cationic nanoparticles as inflammatory inhibitors to treat rheumatoid arthritis Huiyi Liang, Lixin Liu, Jun Shen, Kam W. Leong, Yongming Chen

55. Biofilm-responsive silver nanoassemblies with a biofilm locally amplified bactericidal effect for enhanced treatment against multi-drug-resistant bacterial infections Jiahe Wu, Fangyuan Li, Jianqing Gao, Daishun Ling

56. Enzyme-responsive peptide hydrogel for drug controlled release Lin Qiu, Shuwen Zhou, Pengfei Cui, Xuancheng Du, Qianqian Guo, Jianhao Wang, Pengju Jiang

57. Combination of immunogenic cell death and indoleamine 2,3-dioxygenase inhibition for prostate cancer therapy

253 Jianhua Liu, Xiangru Feng, Chunxi Wang, Jianxun Ding

58. Transmembrane delivery of drugs with graphene quantum dots Jiawei Shen, Zhengyang Xue, Qiying Shen, Qi Wang

59. Anti-angiogenic activity of bevacizumab-bearing dexamethasone-loaded PLGA nanoparticles Jiaxin Liu, Ge Li, Fei Xu, Fengying Sun, Youxin Li, Lifu Luo

60. Stimuli-responsive fluorescence and photoacoustic imaging in the second NIR window for molecule imaging and detection of the tumor Qinrui Fu, Jibin Song

61. Self-assembled oxidation-responsive polyethylene glycol-paclitaxel prodrug for cancer chemotherapy Jiajia Xiang, Quan Zhou, Youqing Shen

62. Hypoxia-targeting microrobots for magneto/optics-actuated efficient tumor ablation Jiehua Xing, Ting Yin, Yingmei Luo, Aiqing Ma, Ze Chen, Baozhen Zhang, Yingnian Lv, Mingbin Zheng, Lintao Cai

63. Polymerization inside Living Cells Jin Geng, Weishuo Li, Yichuan Zhang

64. Visualizable polypeptide thermogel for theranostics of orthopedic diseases Jinfeng Sun, Jianxun Ding, Xuesi Chen

65. Self-assembled triptolide prodrug enveloped by mannose modified erythrocyte membrane for targeting and treatment of rheumatoid arthritis Jing Li, Sanpeng Li, Ping Gong, LinTao Cai

66. Enhanced ROS-responsive polymeric micelles based on SN38-polymer conjugates for efficient cancer therapy Jing Liu, Jiajia Xiang, Youqing Shen

67. Facile construction of shape-regulated curcumin-based supramolecular self-assemblies as a versatile platform for drug control and release Longhai Zhuo, An Na, Jing Yang, Bai Yang

68. Synthesis of novel anti-ACQ functional heptamethine cyanine dyes based on click-activated large steric hindrance and their application in tumor imaging in vivo Jingkai Gao, Jialin Zhou, Xiaohan Gao, Xianghan Zhang

69. Synergistic immunological responses induced by near-infrared photo-therapy using versatile single-walled carbon nanohorns as a theranostic agent Jingxing Yang, Mengfei Hou, Wenshe Sun, Chunfu Zhang

70. Multipronged design of polymeric nanodrug with microenvironment-driven cascaded responsive for imaging-guided combined chemo-photothermal therapy Yang Xia, Luo Zhong, An Jinxia, Gao Hui

71. Hydroxyethyl starch based smart nanoparticles for cancer treatment

254 Jitang Chen, Zifu Li, Xiangliang Yang

72. Controlled release of anti-tumor doxorubicin targeting mitochondria Ju Guo, Lijing Fang

73. Polysaccharide-based nanocomposite hydrogel and its application for combinational cancer therapy Juan Li, Yijun Hao, Yuqing Liang, Xiaoyi Sun

74. X-ray-responsive polypeptide nanogel for enhanced chemo-radiotherapy Juan Wang, Baosheng Lia, Jianxun Ding, Weiguo Xu

75. Polymeric prodrug-based therapeutic nanoreactor with tumor-specific activation for cooperative cancer therapy Junjie Li, Zhishen Ge, Kazunori Kataoka

76. Tumor-targeted pH-sensitive hyaluronic acid-orthoester polymeric micelles for drug delivery Xiaoxue Ren, Fei Wang, Hui Sun, Lipeng Qiu, Huijie Zhang, Kai Gong

77. Encapsulation of persistent luminescence phosphors and chromogenic agent into hollow mesoporous silica nanocarrier for fingerprints detect Kai Song, Haifeng Li, Yiqing Hu, Jingbo Yu, Han Yu, Jingang Mo

78. Synthesis of interior-functionalized drug-binding dendrimers for cancer drug delivery Kai Gao, Xinhao Fang, Zhuxian Zhou, Xiangrui Liu, Jianbin Tang, Youqing Shen

79. Synthesis of fluorophore-cored polylysine dendrimers as dendritic fluorescent probes for tumor imaging Kaiqi Wang, Zhuxian Zhou, Hailin Cong, Youqing Shen

80. Linear dendritic-cisplatin conjugates forming pH-responsive nanovesicles for cancer therapy Kexin Liu, Zhuxian Zhou, Xiangrui Liu, Jianbin Tang, Youqing Shen

81. Macrophage membranes coated immunomodulator for enhanced cancer immunotherapy Keke Lian, Xiqin Yang, Yingping Zeng, Yanan Tan, Yu Tong, Hong Yuan, Fuqiang Hu

82. A broad-spectrum ROS-eliminating nanomedicine for targrted therapy of asthma Lanlan Li, Jianxiang Zhang

83. Targeted oxygen-enhanced photodynamic therapy for inducing anti-tumor immunity Lanlan Liu, Ruijing Liang, Huamei He, Haimei Zhou, Lintao Cai

84. Aggregation mechanisms of graphene oxide and graphdiyne oxide: experimental and theoretical studies Xiaoxiao Deng, Rongjian Sa, Tingting Zheng, Jian Liu, Huibiao Liu, Yuliang Li, Lee Jia

85. The impact of patent system differences on the development of nano-drug innovation based on patent data taking CN, US and JP as examples Honga Zhang, Ying Liu, Ji Li

86. Facile fabrication of silk fibroin-CpG oligodeoxynucleotides nanoparticles for enhanced immunostimulation

255 Huijie Zhang, Li Lai, Jinghua Chen

87. Scintillator-conjugated GNRs for CT/PA imaging-guided photothermal therapy and X-ray induced photodynamic therapy Li Luo, Hongmin Chen

88. Hollow MnO2 nanoparticles/enzyme hybrid as self-cascade nanozyme for glucose monitoring in human serum Lijuan Chen, Haiyan Gao, Yan Bai, Meiyun Wang

89. Cathepsin b responsive peptide-purpurin conjugates for cancer sonotheranostics Lisi Xie, Qixuan Dai, En Ren, Yunlu Dai, Gang Liu

90. A tumor-specific amplification of oxidative stress with triggered drug release nanoparticle for cancer therapy Li Yang, Weihua Zhuang, Gaocan Li, Yunbing Wang

91. Rational design and delivery of a γ-glutamyl transpeptidase-responsive 7-ethyl-10-hydroxy camptothecin prodrug Lingqiao Hao, Quan Zhou, Jiajia Xiang, Ying Piao, Zhuxian Zhou, Xiangrui Liu, Jianbin Tang, Youqing Shen

92. Multidentate succinylated heparin monolayer coated supermagnetic nanoparticles: A stable, biocompatible contrast agent for T2-weighted magnetic resonance imaging with ultrahighT2 proton relaxivity Manman Xie, Christopher J. Butch, Ziyang Wang, Shuming Nie, Qian Lu and Yiqing Wang

93. Oral targeted delivery by nanoparticles enhances efficacy of an hsp90 inhibitor by reducing systemic exposure in murinemodels of colitis and colitis-associated cancer Mei Yang, Fang Zhang, Mingzhen Zhang

94. Multifunctional Fe@γ-Fe2O3@BTO nanocomposites with enhanced magnetic and photoconversion effects for imaging-guided photothermal cancer therapy Meifang Wang, Zhiyao Hou, and Jun Lin

95. Abstract preparation of doxorubicin/indian ink-loaded targeted multifunctional molecular probe and in vivo ultrasound/photoacoustic imaging Meng Wu, Qi-Chao Zheng

96. Boosting the photoconversion performance of NdVO4 nanocrystals for solar-driven photocatalyst and near infrared light-activated Phototherapy Mengyu Chang, Zhiyao Hou, and Jun Lin

97. A simple strategy for preparation of nanoformulations as multifunctional platform for imaging and chemo-photodynamic cancer therapy Xuedi Gao, Yujie Lu, Bin Wu, Ming Cao, Ru Xia, Jiasheng Qian

98. A pH-sensitive nano transdermal delivery system for methotrexate in rheumatoid arthritis treatment Tingting Guo, Xu Kang, Mingming Chang

256 99. Synthesis, characterization and self-assembly of lanthanide-doped nanocrystals Mingzhu Zhou, Qianqian Su

100. Hydrophobic and hydrophilic targeting ligand modified low molecular weight polyethyleneimine for hepatic cancer gene therapy Mingzhuo Cao, Nasha Qiu, Ying Piao, Youqing Shen

101. Design of poly (photosensitizes) for photodynamic therapy Nan Zheng

102. Cucurbit[8]uril-mediated supramolecular assembly for light controlled drug release Dejun Ding, Ni Cheng

103. Hucmsc-derived exosomes ameliorate osteopenia by restoring function of recipient bmscs through inhibiting mtor signaling Ning Zhang, Yong Hu, Weiguo Xu

104. Peg-detached arsenic trisulfide nanoparticle bound with platinum drug for synergistic therapy of hepatoma Pan Zheng, Weiguo Xu, Gao Li

105. Targeted therapy of breast cancer with pH-induced charge reversal mesoporous silica- doxorubicin nanoparticles Yang CB, Cui L, Shen YQ, Shen PH, Liu WT, Li JX, Yang YP

106. pH sensitive charge‐reversal nanoparticles for tumor‐triggered targeting uptake and enhanced anticancer drug delivery Lin Li, Kaoxiang Sun, Peng Zhang

107. An NIR-absorbing nanoparticle system loaded with TLR-7/8 ligand for combinational photothermal immunotherapy Poming Chen, Wenyu Pan, Chengyu Wu, Chingyn Yeh, Pokai Luo, Yumiao Liu, Chunju Chou, Hsingwen Sung

108. Rational design of pH-Activatable Nanoparticles for dual-stage targeting of early endosome and mitochondria to promote photodynamic therapy Tong Qi, Binlong Chen, Qiang Zhang, Yiguang Wang

109. Improved tumor therapy via a magnetism/laser-heating auxiliary cascading nanosystem delivery based on three-step strategy Jialiang Lin, Qingqing Ying, Binlong Chen, Haoran Zhang, Dong Mei, Bing He, Hua Zhang, Wenbin Dai, Xueqing Wang, Yiguang Wang, Qiang Zhang

110. Nonviral ferrimagnetofection based stem cell engineering for highly efficient post-stroke recovery Qiyue Wang, Fangyuan Li, Daishun Ling

111. A nanosensor based on reusable silver plasmonic nanoarray for sweat detection Quanying Fu, Xuemeng Li, Yingshuting Wang, Li Zhang, Jianhua Zhou

112. Facile fabrication of fullerene-based manganese chelates as potential mri contrast agents

257 Zhenfeng Zang, Yuke liu, Yanjie Liu, Hezhong Wang, Qingnan Wu, Rui He

113. Smart gold nanocages for oxygen-boosted and immuno-stimulative photodynamic therapy Ruijing Liang, Lanlan Liu, Huamei He, Shengping Zhang, Lintao Cai

114. Lipos-gold nanocages for photothermally-triggered drug release and antitumor therapy Zhiqun Han, Shengping Zhang, Huamei He, Ruijing Liang, Lintao Cai

115. Application of copper (Ⅱ)-loaded nanogel as an adjuvant to enhancing disulfiram antitumor efficacy Rui Sun, Yu Geng, Youqing Shen

116. Rapeseed protetin-based biopolymer for enhanced drug delivery in cancer chemotherapy Rui Xue Zhang, Zhigao Wang, Xiao Yu Wu

117. NIR-Ⅱ triggered drugreleased of 2D tungsten nitride nanosheets-based hydrogel for treatment of cancer Senfeng Zhao, Qunfang Xu, Qianqian Xu，Liu Deng and You-Nian Liu

118. Glycopolymers containing near-infrared-II molecular fluorophore for biological imaging and chemo-photothermal combination therapy of cancers Shangyu Chen，Pengfei Sun, Quli Fan

119. O2 production enhancement induced by Gd2O3:Yb,Er,Mn upconverting nanoparticles: Towards amelioration of tumor microenvironment and highly effective photodynamic therapy Shaoxin Song, Xiaoqian Zhou, Wei Wang

120. Cancer cell membrane coated immune-adjuvant nanoparticles for tumor photothermal immunotherapy Shengxian Li, Heping Qiu, Jianhua Liu, Jixue Wang, Jinghai Hu, Chunxi Wang

121. Anti-proliferation and migration activities of hyaluronic acid modified liposome co-loaded with doxorubicin and epalrestat Shiyan Dong, Xiangshi Sun, Chunmiao Yang, Xinyu Wang, Xiaolong Zheng, Jing Xie, Lesheng Teng

122. Pt-cus janus for synergistic sonodynamic and photothermal cancer therapy Shuang Liang, Ziyong Cheng and Jun Lin

123. VAP-alginate-PVA hydrogels facilitates the differentiation of NPC towards oligodendrocytes in 3D neural spheroids Siqi Ma, Zhaoqing Cong, Huan Chen, Han Wen, Weiya Chen, Feifei Yang, Yonghong Liao

124. Poly(N-oxide) as an omnipotent drug carrier for highly potent cancer chemotherapy Siqin Chen,Yin Zhong, Jiajia Xiang, Honggang Cui, and Youqing Shen

125. Reduction-responsive carbon dots for real-time ratiometric monitoring of anticancer prodrug activation in living cells Tao Feng, Peng Li, Wei Huang

126. X-ray induced persistent luminescence for tumor imaging and photodynamic therapy

258 Tianhang Shi and Hongmin Chen

127. Intratumoral delivery of CCL25 enhances immunotherapy against triple negative breast cancer by recruiting CCR9+ Tcells Hongmei Chen, Xianzhu Yang, Yong-Guang Yang and Tianmeng Sun

128. A multimodal imaging-guided nanoplatform based on mesoporous silica nanoparticles for synergistic chemo-photothermal therapy Tingting Li, Yue Geng , Yi Feng , Xiaoxue Xie , Jing Wang , Zhongyuan Chen , Hanxi Zhang , Chunhui Wu , Yiyao Liu , Hong Yang

129. Co-delivery of anti-PD-L1 siRNA and CpG with Roller Microneedle Electrode Array (RMEA) for cancer immunotherapy Tongren Yang, Dong Huang Chunhui Li, Zhihong Li, Yuanyu Huang

130. PVA nano/microgels as an emerging platform for cancer therapy Xingmei Chen, Haishi Qiao, Dechun Huang, and Wei Chen

131. Enzyme-instructed self-assembly in situ of small molecules for targeting cancer cells in vivo through bioorthogonal reactions Wei He, Xin Jiang, Zhenguo Liang, Hong Pan, Wenjun Li, Lintao Cai

132. Combined oxidative stress therapy and photothermal therapy of tumors by copper phosphate nanospheres Bing Li, Ning Nie, Zhentao Hua, Wei Wang

133. Biomimetic formulation engineering for anticancer therapy Wei Wei, Guanghui Ma

134. Synergistic regulation of macrophage transformation for inhibition of tumor progression Weiguo Xu, Xiuli Zhuang, Jianxun Ding

135. Multifunctional drug carrier for precise two-photon tumor localization and effective tumor therapy Weihua Zhuang, Boxuan Ma, Jun Hu, Li Yang, Gaocan Li and Yunbing Wang

136. Fabrication and characterization of the borneol-citral loaded pickering emulsions stabilized by amine-functionalized silica nanoparticles and their antibiofilm efficacy against microbial pathogens Wen Wang, Jianyu Su

137. In vitro synchronous release behaviour, pharmacokinetics and its release correlation in vitro and in vivo of ph-sensitive and time-dependent polymer formula of tasa colon targeted pelletse Lijun Song, Wenchang Zhao

138. Biomimic black phosphorus/upconversion nanoparticles for near-infrared fluorescence-guided bone repair Wenhao Dai, Haifeng Dong, Xueji Zhang

139. Gadolinium-doped rose bengal nanodots for MR/fluorescence imaging-guided radio- and photodynamic therapy

259 Wenjing Sun and Hongmin Chen

140. Controlled and targeted drug delivery by UV-responsive nanocopomsites for safer urethral carcinoma infusion therapy Hong Dai, Zhihai Yu, Chunmei Wang, Yaochuan Guo, Kun Yu, Xiao Huang

141. A hyaluronic acid-based nanotheranostic iron oxide nanoparticles for MRI-guided tumor photothermal therapy Xiaodan Xu, Xiaoxuan Zhou, Bing Xiao, Yong Chen, Zhuxian Zhou, Xiangrui Liu, Hongjie Hu, Jianbin Tang, and Youqing Shen

142. Epicatechin-based nanotheranostic agents for MR imaging and photothermal therapy Xiaoxuan Zhou, Xiaodan Xu, Bing Xiao, Hongxia Xu, Yuxin Han, Yue Qian, Feidan Yu, Zhuxian Zhou, Xiangrui Liu, Hongjie Hu, Jianbin Tang, Youqing Shen

143. ZnO@ZIF-90@DOX multifunctional core-shell nanoparticles for pH-responsive drug Xiao Xiao, Ziyong Cheng, Jun Lin

144. Preparation and evaluation of antibacterial activity of litsea cubeba oil microemulsions Xiaofeng Meng, Han Hu, Jianyu Su

145. Förster resonance energy transfer-based dual-modal nanoprobes for pH sensing Xiaohan Gao, Zhiqing Gao, Yingdi Tang, Xianghan Zhang, Yuqiong Xia

146. Nanoparticle-mediated immunogenic cell death enables and potentiates cancer immunotherapy Xiaopin Duan, Christina Chan, Wenbo Han, Nining Guo, Ralph R. Weichselbaum, Wenbin Lin

147. Exenatide-loaded zein nanoparticles and oral hypoglycemic efficacy in db/db mice Xiaoyan Bao, Ping Yao

148. Bio-orthogonal targeting strategy mediated enhancement for NK cells cytotoxicity against tumor cells Xin Jiang, Hong Pan, Zhenguo Liang, Wei He, Yingmei Luo, Ze Chen, Zhihong Sun, Lihua Zhou, Haimei Zhou, Shengping Zhang, Jiehua Xing, Ping Gong, Mingbin Zheng, Wenjun Li, Lintao Cai

149. Pro-apoptotic peptide-decorated protein nanoparticle for cancer therapy Dongmei Wang, Li Chen, Dan Yu, Moyuan Qu, Wei Xia, Xingang Guan

150. Asymmetric heterocycle induced tunable emitting fluorescence of graphitic carbon nitride QDs for cell imaging and QLED Xingchen He, Ziyang Wang, Manman Xie, Qian Lu, Yiqing Wang

151. RGD modified Bi2Se3 nano foam as an intracellular delivery system for anti-exocytosis- enhanced cancer therapy Xinghua Yu, Seung Wuk Lee, Bilu Liu

152. The study on esterase responsive polymers with different side chains Peiwen Xing, Guowei Wang, Youqing Shen

153. siRNA loaded nanoparticles suppress tumor growth via downregulating cancer cell derived

260 exosomal microRNA XinxinZhang, Shufang He, Yunqiu Miao, Yong Gan

154. Co-delivery of antigen and CCR7 plasmid DNA by glycolipid polymer micelles results in dramatically enhanced cellular immune responses Xiqin Yang, Keke Lian, Yingping Zeng, Hong Yuan, Fuqiang Hu

155. Mechanism of targeting in solid tumors with polymeric micelles Xiqin Yang, Keke Lian, Tong Yu, Hong Yuan, Fuqiang Hu

156. Reactive oxygen species (ROS)-responsive charge-switchable nanocarriers for gene therapy of metastatic cancer Xin Liu, Zhuxian Zhou, Youqing Shen

157. A photo-activable polymeric nanosphere: Self-assembled linear-dendritic copolymer for photodynamic therapy Xiuli Zheng, Dayi Pan, Kuo Luo

158. A novel multi-functional FePt/BP nanocomposites for chemotherapy, photothermal/dynamic synergistic cancer therapy Xiuxiu Yao, Dongsheng Zhang, Xiuwen Zheng, Qingyun Liu

159. A dense poly(ethylene glycol) coated protein nanocages improves brain-penetration and doxorubicin efficacy in brain metastases of lung carcinoma following local administration Xuanrong Sun, Divya Rao, Seung Woo Chung, Xiaoxin Wang, Daiqin Chen, Hao Su, Sidd Shenoy, Buwei Huang, Honggang Cui, Justin Hanes, Jung Soo Suk

160. Real-time and non-invasive tracking of stem cells with highly bright AIE nanoprobe in treatment of radiation-induced skin injury Cuihong Yang, Xue Zhang, Chunhua Ren, Jianfeng Liu

161. Al plasmonic nanoarray biosensor for real-time and polychromatic monitoring of cell adhesion Xuemeng Li, Quanying Fu, Li Zhang, Yingshuting Wang, Jianhua Zhou

162. S1PR1 antagonist modifiedpolymer micelles for targeting tumorcells and tumor associated macrophages Xueqing Zhou, Xuan Liu, Xuwei Shang, Hong Yuan, Fuqiang Hu

163. MMP-9 Responsive supramolecular co-assembled hydrogel targeting myocardial infarction for cardiac remodeling therapy Zhanpeng Wen, Shaodan Ma, Yanbin Cai, Minsheng Chen

164. Enzyme-instructed self-assembled peptides for enhancement of antitumor activity by histone deacetylase inhibitors Yang Gao, Xue Zhang, Cuihong Yang, Chunhua Ren

165. Covalent organic framework-based nanosheets for fluorescence secondary-amplification bioimaging and photothermal therapy in tumor Yang Liu, Wei Wang, Qiang Wu, Zhi Yuan

166. Thermogelsof different chiral polypeptides regulateimmune microenvironmentof tumors

261 Yang Liu, XiangruFeng, XiuliZhuang, JianxunDing, XuesiChen

167. Novel injectable thermosensitive hydrogel scaffold for tumor multicellular spheres generation Yang Liu, Wanling Xiong, Yuli Yin, Yunjuan Wang, Yi Wang, Huan Wang

168. Tunable pH-sensitive lipid conjugated dexamethasone for anti-rheumatoid arthritis Yang Xu, Jingqing Mu, Zunkai Xu, Haiping Zhong, Ziqi Chen, Shutao Guo

169. An m-cell targeting yeast capsule loaded with biomimetically mineralized nanoscale OVA@Al-MOF to overcome multiple barriers of intestinal epithelium for oral vaccination Yangbao Miao, Kuanhung Chen, Chunyu Shang, Hsingwen Sung

170. Ultra-small biocompatible longan polysaccharide stabilized platinum nanoclusters for glucose detection Yanshuai Cui, Shengfu Chen, Longgang Wang

171. Mesoporous silica-encapsulated gold nanorods as a drug delivery platform for the treatment of parkinson’s disease Yao Liu, Daoming Zhu, Jingshan Luo, Wei Liu, Tongkai Chen

172. Physicochemical and controlled release properties of chitosan/curcumin/zein nanoparticles generated by electrospray Yaowen Liu, Yihao Wang, Saeed Ahmed, Wen Qin, Kangju Lee

173. Sirna delivery using folate receptor-targeted reduction-responsive liposomes Yarong Zhao, Luotong Liu, Fanchao Meng, Jing Xie, Robert J. Lee, Lesheng Teng

174. Reversal of Multi-drug-resistant lung cancer via ultrasonic-mediated drug delivery Tian Ye, Zhang Yang, Liu Gang

175. Heparin modified pH-sensitive liposomes with drug combination encapsulated as chemoimmunotherapy for the melanoma treatment Yi Chen, Jianqing Peng, Jinzhuan Xu, Qiuxiao Xiao, Xiangchun Shen

176. A novel preparation of HA/PEI/DNA nanocomposites by microfluidics Yihuai Shen, Zhuxian Zhou, Xiangrui Liu, Jianbin Tang, Youqing Shen

177. Intelligent IL12 nanoparticles engineered CAR T cells for enhanced immunotherapy of solid tumor Yingmei Luo, Hong Pan, Jiehua Xing, Aiqing Ma, Ze Chen, Ting Yin, Mingbin Zheng, Baohong Li, Lintao Cai

178. A dual-mode biosensor of Au nanorod-quantum dots satellite nanoassembles Yingshuting Wang, Xuemeng Li, Quanying Fu, Jianhua Zhou

179. Facile construction of star polymer micelles with pseudo crosslinked structures for drug delivery Yinwen Li, Hongzhi Lu, Longjiang Yu, Mingzhu Hu, Shoufang Xu

180. The effects of the surface properties of a gold nanorod on its in vitro/vivo toxicity against cancer cells

262 Yong Huang, Xia Dong, Wanru Tao, Wei Li

181. Fabrication of the camptothecin drug delivery system based on the hydrophilic hollow silica nanospheres Yongsheng Ji, Shuhui Song, Ruihong Lv, Mingzhou Cao

182. Stapling of cell penetrating peptides for highly efficient cell-and-tissue penetration Yuan Tian, Mengzhen Shi, Rui Tang

183. Engineering oral subunit vaccine to sequentially overcome mucus and epithelial transport barriers against H.pylori infection Yuandong Zhang, Haibo Li, Quanming Zou, Xun Sun

184. Tumor-targeting peptide functionalized PEG-PLA micelles for efficient drug delivery Yue Cai, Zhuomin Xu, Xuanrong Sun

185. Development copper complex (Cu(OPDEA)2) combination with disulfiram for tumor treatment Yu Geng, Rui Sun, Yin Zhong, Youqing Shen

186. Metal-organic frameworks as delivery vehicles for encapsulation and release of specific molecules Yuhang Liu, Zhuxian Zhou, Liming Jiang

187. p(NIPAM-r-HPMA) modified thermo-sensitive liposomes for hyperthermia-tuned quick drug release and chemotherapy Yulin Mo, Hongliang Du, Qiang Zhang, Yiguang Wang

188. Magnetic manganese oxide sweetgum-ball nanospheres with large mesopores regulate tumor microenvironments for enhanced tumor nanotheranostics Yushuo Feng, Hongmin Chen

189. Dual neurovascular targeting platform for stroke based on platelet-like nanoparticles loaded with ginkgolide B Yuxiang Fei, Yangnan Su, Yunman Li, Jianping Zhou, Wei Wang

190. Near-infrared light triggered tumor oxygenation with a multifunctional nanoemulsion for imaging-guided enhanced radiotherapy of cancer Yuzhu Yao, Chong Wang, Zifu Li, Jun Hu, Xiangliang Yang

191. Platelet inhibition mediated by perfluocarbon nanoparticles to boost tumor therapy efficacy Zaigang Zhou, Baoli Zhang, Jianliang Shen, Yiqiao Hu, Jinhui Wu

192. Nanophotosensitizer engineered CAR-T cells with photothermal-triggered modulation for solid tumors therapy Ze Chen, Hong Pan, Yingmei Luo, Ting Yin, Ruijing Liang, Aiqing Ma, Jiehua Xing, Baozhen Zhang, Mingbin Zheng, Lintao Cai

193. Dual pH-sensitive nanomedcine co-deliver NF-κb inhibitor and PD-1 immune checkpoint for antitumor immunotherapy Zecong Xiao, Zhenwei Su, Xintao Shuai

263 194. One-click combination of precision chemotherapy and photodynamic therapy Zheng Luo, Yunlong Wu

195. Salmonella YB1 carrying pH-responsive nanoparticles based on bioorthogonal strategy for tumor-targeted treatment Zhenguo Liang, Zhongsheng Zang, Xin Jiang, Guanjun Deng, Wei He, Fuming Chen, Ze Chen, Qian Ren, Hong Pan, Ping Gong, Lihua Zhou, Wenjun Li, Chenli Liu, Lintao Cai

196. A novel fluorescence probe for the detection of hypochlorous acid in cancer cells Lu Tian, Xiuwen Zheng, Zhichao Dai

197. ROS-responsive microparticles encapsulating superoxide dismutase for alleviating acute inflammation-induced injury Zhicheng Le, Zhitao Hu, Zhijia Liu, Yongming Chen

198. Construction of fluorescence resonance energy transfer probe based on quantum dot magnetic nanomicrospheres and detection of carcinoembryonic antigen Xuemeng Li, Ahmned Mohamed, Wantao Tang, Zhidong Xiao

199. N-oxide liposomes for the delivery of SN38/CPT11 nanoparticles Zhihao Zhao, Yupu Feng, Youqing Shen

200. Size-controlled flash fabrication of coordination hyaluronic acid nanoparticles for cancer theranostic application Zhijia Liu, Zhicheng Le, Lilong Sun, Yongming Chen

201. Dynamic pH-responsive polymersomes based on amphiphilic graft copolymers: a dissipative particle dynamics study Zhonglin Luo, Wanping Wang, Biaobing Wang

202. Regorafenib-activated polypeptide prodrug of TGF-β inhibitor for synergistic therapy of advanced colorectal cancer Zhongmin Li, Weiguo Xu, Jianxun Ding

203. IGF1 receptor targeted protein-based magneto-optical nanoassembles for magnetic resonance/magnetic particle/NIR-II fluorescence multimodal imaging of deep pancreatic cancer Duyang Gao, Dehong Hu, Zonghai Sheng, Hairong Zheng

204. Chloroquine primes hepatocellular carcinoma with desmoplasia for membrane-bound full- length trail Zimo Liu, Xiangrui Liu, Zhuxian Zhou, Jianbin Tang, Youqing Shen

205. A novel fept-based versatile nanocomposites for tumor chemo-photothermal co-therapy and multimodal imaging Zunfu Hu, Dongsheng Zhang, Xiuxiu Yao, Xiuwen Zheng

264 各位 CASNN 2019 的参会者：我们为所有摘要都准备了海报展位，原则上所有参会人均可参加海报展，请各位参与者认真准备。海报内容须详实，图文并茂，便于与其他与会人员交流。海报展中将评选出若干优秀者授予最佳海报奖。为了保证评选过程的公正透明，我们在会议资料袋中为每位参会人准备了 10 张选票贴纸，在海报展过程中，大家可将贴纸贴于自己认可的海报上，在海报展结束后，我们将会统计每张海报上的贴纸数，以此排序评选出本次 CASNN 2019 大会的最佳海报奖。小编在此提醒大家，只有多与参观者交流，多向大家介绍自己的工作才能“骗”到观众手中的选票哦！因此，请各位参展者各展所长，这是一场人人都是评委的海报展。另外，我们将会在海报展现场为大家准备一些饮品，希望大家在推杯换盏中增进交流，获得灵感。

Dear participants of CASNN 2019: We have prepared poster booths for all abstracts, and in principle, all participants can participate in the poster exhibition, so please prepare carefully. The content of the poster must be detailed and illustrated so as to facilitate communication with other participants. A number of outstanding ones will be selected for the top poster awards in the poster exhibition. In order to ensure the fairness and transparency of the selection procedure, we have prepared 10 vote stickers for each participant in the conference kit. During the poster exhibition, you can paste the stickers on the posters you prefer. We will count the number of stickers on each poster to rank and select the top poster awards for this CASNN 2019 conference. Kindly remind: only more communication with viewers and more introduction of your work to others can "cheat" morevotes! Therefore, hope each participant would give full play to his/her strong point, and this will be an exhibition in which everybody is a judge. In addition, we will prepare some drinks at the poster exhibition. Hope that everyone would have good communication and draw good inspiration.Have a good time!

265 资助单位：

浙江省自然科学基金委

浙江大学化学工程国家重点实验室浙江大学教育部生物工程重点实验室

冷泉港生物科技股份有限公司

富士光科技(苏州)有限公司

厦门福流生物科技有限公司

纳米医药研究整体解决方案

锘海生物科学仪器（上海）股份有限公司

266

推动纳米医学发展的变革性思维 Transform Nanomedicine with Breakthrough Thinking

主办单位：中美纳米医学与纳米生物技术学会（CASNN）

承办单位：浙江大学杭州市萧山区人民政府

协办单位：萧山区委人才办萧山区投资促进局萧山科技城管理局化学工程国家重点实验室（浙江大学）浙江理工大学浙江大学生物质化工教育部重点实验室冷泉港生物科技股份有限公司浙江省药学会生物制药专业委员会浙江湘湖影视文化有限公司浙江原始资本管理有限公司