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Metal Organic Framework-Coated Gold Nanorod As an On-Demand Drug

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Metal Organic Framework-Coated Gold Nanorod As an On-Demand Drug Huang et al. J Nanobiotechnol (2021) 19:219 https://doi.org/10.1186/s12951-021-00961-x Journal of Nanobiotechnology RESEARCH Open Access Metal organic framework-coated gold nanorod as an on-demand drug delivery platform for chemo-photothermal cancer therapy Junfeng Huang1,2†, Zhourui Xu3†, Yihang jiang3, Wing‑cheung Law4, Biqin Dong5, Xierong Zeng1, Mingze Ma3, Gaixia Xu3*, Jizhao Zou1* and Chengbin Yang3* Abstract Chemo‑photothermal therapy based on nanoparticles has emerged as a promising strategy for cancer treatment. However, its therapeutic efcacy and application potential are largely subjected to the uncontrollability and biotoxic‑ ity of functional nanoplatforms. Herein, a novel biocompatible and biodegradable metal organic framework (MOF), which was constructed by growing crystalline zeolitic imidazolate framework‑8 on gold nanoroad (Au@ZIF‑8), was designed and fabricated for efcient drug loading and controlled release. Owing to the large surface area and guest‑ matching pore size of ZIF‑8, doxorubicin (DOX) was successfully loaded into the Au@ZIF‑8 with a high drug load‑ ing efciency of ~ 37%. Under NIR light or weakly acidic environment, the ZIF‑8 layer was quickly degraded, which resulted in an on‑demand drug release in tumour site. More importantly, under the irradiation of near infrared (NIR) laser, highly efcient cancer treatment was achieved in both in vitro cell experiment and in vivo tumour‑bearing nude mice experiment due to the synergistic efect of photothermal (PTT) therapy and chemotherapy. In addition, the in vivo study revealed the good biocompatibility of Au@ZIF‑8. This work robustly suggested that Au@ZIF‑8 could be further explored as a drug delivery system for chemo‑photothermal synergistic therapy. Keywords: Metal organic framework, Gold nanorod, Photothermal therapy, Drug delivery, Biocompatible Background feld in the past few decades, several cancer therapy Cancer, as the most dreadful disease in the world, was approaches, such as chemotherapy [2], surgery [3], and responsible for nearly one-ffth of human death [1]. radiotherapy [4], have been developed and used in clini- Owing to the great eforts contributed to the biomedical cal settings. As a major cancer therapeutic approach, the chemotherapy still faces many challenges in clinical prac- tice, such as limited therapeutic efcacy, poor patient *Correspondence: [email protected]; [email protected]; [email protected] compliance and severe toxic-side efects [5]. In recent †Junfeng Huang and Zhourui Xu contributed equally to this work years, thanks to the encouraging progress of nanotech- 1 Shenzhen Key Laboratory of Special Functional Materials & Shenzhen nology-based combined therapy [6], which integrated Engineering Laboratory for Advance Technology of Ceramics, College of Materials Science and Engineering, Shenzhen University, diferent components, such as drugs, targeting molecules, Shenzhen 518060, China biodegradable polymers, into a single nanoplatform, has 3 Guangdong Key Laboratory for Biomedical Measurements emerged as a potential solution to overcome the afore- and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen 518060, China mentioned hurdles. Te synergism of various compo- Full list of author information is available at the end of the article nents not only contributed to a remarkable super-additive © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Huang et al. J Nanobiotechnol (2021) 19:219 Page 2 of 13 therapeutic efect, but also signifcantly reduced the exceptional large surface area and tunable inner cavity. adverse efects [7–9]. Among diverse types of combina- Among them, zeolitic imidazolate framework-8 (ZIF- tions, chemo-photothermal therapy has attracted special 8) with low-toxic Zn 2+ and 2-methylimidazole (2-MIN) attentions for four major reasons: 1) hyperthermia could as the basic units, was recognized as a biocompatible potentially sensitize tumor to chemo-drugs, 2) hyper- and acid-responsive drug carrier [31]. In addition, the thermia could enhance the cellular uptakes of drug car- fabrication process requires no toxic additives with fac- riers, 3) the localized drug release can be triggered by ile synthetic approach, which ensure the safety use and the photothermal efects [10], and 4) chemo-drug could reliability of ZIF-8 nanostructures. Inspired by its unique efciently interrupt the cell metabolism and soften the properties, we envisaged a great opportunity to exploit heat shock response upon hyperthermia [11]. All these the full potential of chemo-photothermal therapy by features have enabled us to obtain satisfactory outcomes combining AuNR and ZIF-8 shell materials. of cancer therapy with reduced side efects. Nevertheless, In this work, a multifunctional nanoplatform com- efciency of chemo-photothermal therapy depends on posed of AuNR, ZIF-8 and doxorubicin (DOX) were the design and fabrication of nanoplatforms. Currently, successfully designed and synthesized for chemo-pho- core–shell nanostructures have become a gold standard tothermal synergistic therapy. Specifcally, a core–shell due to the high fexibility to control the size, morphology, formulation of Au@ZIF-8 was prepared by growing and individual function [12]. Hence, this work is focused ZIF-8 material onto individual AuNR with the guidance on selecting safe and efcient functional components to of Polyvinylpyrrolidone (PVP) polymer. Ascribed to the fabricate a multifunctional nanoplatform for chemo-pho- remarkable surface area and guest-matching pore size tothermal therapy. of ZIF-8, an exceptional drug loading efciency of ~ 37% With the continuous eforts in photothermal applica- were achieved in Au@ZIF-8/DOX formulation. Further- tions, various types of photothermal agents have been more, the materials characteristics results demonstrated explored, including copper chalcogenide nanocrys- that the weak acidic condition and photothermal efect tals [13], nanocarbons [14], gold-based nanostructures promoted degradation of ZIF-8 shell layer, which resulted [10, 15], black phosphorous[16], and organic dyes [17]. in an on-demand controlled drug release. Te Au@ZIF-8 Among them, gold-based nanomaterials have more showed a high photothermal efect upon NIR irradiation, excellent performance for clinical translation owing to and the generated heat not only directly killed cancer its promising photothermal responses and bio-inertness cells but also synergistically promoted the DOX release, [18–20]. Up to now, four clinical trials (ClinicalTrials.gov which exhibited better performance for inhibiting cell identifer: NCT00848042, NCT01679470, NCT02680535 viability than free DOX. Furthermore, in vivo therapeutic and NCT04240639) of photothermal therapy based on results confrmed that the synergistic chemo-photother- gold nanostructures have been endorsed by the National mal by Au@ZIF-8/DOX + NIR achieved much higher Institute of Health Clinical Center (U.S.A), suggesting treatment efcacy than photothermal therapy by Au@ that the great application potential of gold-based nano- ZIF-8 + NIR or chemotherapy by DOX only and even structures. Currently, anisotropic gold nanorod (AuNR) resulted in complete tumor elimination without obvious with tunable optical properties has been demonstrated adverse efect. Tis work provides a novel design of Au@ to be an ideal component for constructing core–shell ZIF-8 nanoplatform for chemo- and photothermal ther- nanoplatform for tumour therapy [21, 22]. When AuNR apy, which can lead to a synergistic therapeutic efect and was used as a photothermal core, on-demand control- hold great promise for future clinical translation. lable drug release from the shell reservoir could be trig- gered by light excitation [23]. However, limited choices Materials and methods have been given for shell materials due to their low drug Materials loading capability, toxic synthetic approaches, time-con- Cetyltrimethylammonium bromide (CTAB) was pur- suming synthesis, and high tendency in causing aggre- chased from Sigma. Tetra-chloroauric acid (HAuCl4), gation [24, 25]. Terefore, in order to achieve the full ascorbic acid (99.0%), silver nitrate (AgNO3), 2-methyl- potential of chemo-photothermal therapy, it is critical to imidazolate (2-MIM), Zinc nitrate hexahydrate, monoso- choose biocompatible, biodegradable, and reliable shell dium phosphate (NaH2PO4), sodium hydrogen phosphate materials. (Na2HPO4), sodium borohydride (NaBH4), polyvinyl Recently, metal–organic frameworks (MOFs),
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