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Near-Infrared Light-Triggered Theranostics for Tumor-Specific Enhanced Multimodal Imaging and Photothermal Therapy

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Near-Infrared Light-Triggered Theranostics for Tumor-Specific Enhanced Multimodal Imaging and Photothermal Therapy Journal name: International Journal of Nanomedicine Article Designation: Original Research Year: 2017 Volume: 12 International Journal of Nanomedicine Dovepress Running head verso: Wu et al Running head recto: Near-infrared light-triggered open access to scientific and medical research DOI: http://dx.doi.org/10.2147/IJN.S137835 Open Access Full Text Article ORIGINAL RESEARCH Near-infrared light-triggered theranostics for tumor-specific enhanced multimodal imaging and photothermal therapy Bo Wu1,* Abstract: The major challenge in current clinic contrast agents (CAs) and chemotherapy is Bing Wan2,* the poor tumor selectivity and response. Based on the self-quench property of IR820 at high Shu-Ting Lu1 concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of Kai Deng3 liposome, we developed “bomb-like” light-triggered CAs (LTCAs) for enhanced CT/MRI/ Xiao-Qi Li1 FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue spe- Bao-Lin Wu1 cifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration. This will result in protection and fluorescence quench- Yu-Shuang Li1 ing. Then, the release of CAs was triggered by near-infrared (NIR) light laser irradiation, Ru-Fang Liao1 which will lead to fluorescence and MRI activation and enable imaging of inflammation. In 3 Shi-Wen Huang vitro and in vivo experiments demonstrated that LTCAs with 808 nm laser irradiation have Hai-Bo Xu1,2 shorter T1 relaxation time in MRI and stronger intensity in FI compared to those without 1Department of Radiology, Zhongnan irradiation. Additionally, due to the high photothermal conversion efficiency of IR820, the Hospital of Wuhan University, injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice 2Department of Radiology, Union Hospital of Tongji Medical College, up to 17 days after NIR laser irradiation. The results indicate that the LTCAs can serve as a Huazhong University of Science promising platform for NIR-activated multimodal imaging and photothermal therapy. 3 and Technology, Department of light triggered, near-infrared light, tumor-specific, multimodal imaging, photo- Chemistry, Key Laboratory of Keywords: Biomedical Polymers, Ministry of thermal therapy, contrast agents Education, Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally Introduction to this work Early diagnosis and proper disease management of tumor, as well as the personalized medicine of tumor, depend on the precise diagnosis of pathological states of tumor. Various noninvasive imaging techniques such as computed X-ray tomography (CT)/ magnetic resonance imaging (MRI)/fluorescence imaging (FI) have been widely applied in diagnosis of tumor in clinical practice.1,2 Since CT, MRI, and optical imaging all Correspondence: Shi-Wen Huang have their own strengths and weaknesses, the combination of these imaging techniques Department of Chemistry, Key Laboratory of Biomedical Polymers, is more preferable for comprehensive and precise information of the tumor. Ministry of Education, Wuhan University, The CT/MRI imaging signal can be modulated with contrast agents (CAs) by 299 Bayi Road, Wuhan 430072, People’s Republic of China absorbing X-ray or shortening the relaxation time of water protons to improve the Tel +86 27 6875 5317 visibility. However, the intrinsic limitation about poor soft tissue resolutions, radia- Email [email protected] tion, and renal toxicity of commercial CAs have limited commercial CAs clinical Hai-Bo Xu application.3,4 In order to improve the modest signal/noise ratio of cancerous tis- Department of Radiology, Zhongnan sues, lots of carriers, which are responsive to such external stimuli as pH,5–7 redox,8 Hospital of Wuhan University, 169 Donghu Road, Wuhan, temperature,9 enzyme,10 and competitive binding,11 have been developed. Neverthe- People’s Republic of China less, acquiring tumor imaging specifically, spatially and temporally has been still a Tel +86 27 6781 2533 Email [email protected] big challenge for CAs. submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2017:12 4467–4478 4467 Dovepress © 2017 Wu et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/IJN.S137835 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Wu et al Dovepress Recently, light-induced release systems of drugs offering high drug encapsulation, and sustained drug release.28 on-demand targeting capability have provided a new unique Liposome was an ideal CAs carrier to clearly display the opportunity for image-guided therapies.12 The photosensi- extent of cancer and monitors the treatment effect in real tive capped delivery systems have attracted much attention time.29,30 In addition, previous research has suggested that CAs owing to their remarkable therapeutic efficacy. Using light to have better MRI contrast effect or stronger fluorescence inten- generate heat has been proven to improve specific release and sity when the CAs were released from the nanoparticles.31 cellular uptake of theranostics agents.13 Upon near-infrared In this account, a novel strategy by using an NIR laser to (NIR) light laser irradiation, the dissipation of absorbed light turn on CT/MRI/FI multimodal imaging and PTT was suc- energy as heat can not only mediate hyperthermia of tumor cessfully developed, based on the self-quench property of with high spatial and temporal resolution but also activate IR820 at high concentrations and different contrast effect the rapid release of contents at the site of interest.14–17 The ability of Gd-DOTA in the inner and outer parts of liposomes. introducing of the light-triggered release systems in CA IR820 was loaded into the core of polyethylene glycol (PEG)- delivery will help to utilize the self-quench property of protected dipalmitoylphosphatidylcholine (DPPC)/distearoyl fluorescence at high concentrations, and has been used for phosphatidylcholine (DSPC) thermosensitive liposomes. optic imaging.18 However, previous reports on light-triggered In addition to the photothermal agent IR820, clinically nanotheranostics mostly focused on cancer treatment. So widely used CA Gd-chelates (Magnevist) for MRI and iodine far, few reports have used light-triggered nanotheranostics compound (Iohexol) for CT were also stored in the core of to improve the imaging effect of clinical use CAs. Because light-triggered CAs (LTCAs), which could result in protec- of that, Gd-DOTA has different contrast effect when it was tion and FI quenching in the systemic circulation. As another 19 inner and outer of liposome, light-triggered nanotheranostics important element, NH4HCO3, which at a high temperature will be one of the most promising delivery to improve the (40°C–42°C) can decompose to CO2 bubbles, was also signal-to-noise ratio of tumor tissue specifically. incorporated into the aqueous compartment of liposomes. Photothermal therapy (PTT) is based on photosensi- The multimodal imaging could be turned on by the release tive agents aimed at localized destruction of cancer cells of CAs triggered by NIR laser. This simple but powerful by conversion of NIR light into heat.20 To date, various strategy for responsive tumor-specific imaging will be very nanosized photothermal agents have been developed for significant for tumor-specific diagnosis and treatment. precise localization and intensity control of heating, which effectively improves the hyperthermia ablation therapy.21,22 Experimental section However, the most current photothermal agents used in the Materials NIR range are inorganic nanomaterials that are not easily DPPC, DSPC, and 1,2-distearoyl-sn-glycero-3-phospho- excreted in biological environment. Thus, it is necessary to ethanolamine-N-[methoxy(polyethylene glycol)] (DSPE- develop NIR-absorbing organic nanomaterials to reduce the PEG) was purchased from Shanghai Advanced Vehicle long-term risks of PTT. IR820 (new indocyanine green) is Technology Co., Ltd. (Shanghai, People’s Republic of China). a sort of cyanine dye, which has more stability under differ- Magnevist was purchased from Yangtze River Pharmaceuti- ent temperatures, longer tissue retention time, and stronger cal Group (Nanjing, People’s Republic of China). Iohexol fluorescent signals.23 IR820 generates sufficient heat upon was purchased from GE Healthcare (Dublin, Ireland). All NIR laser irradiation to create a cytotoxic effect, which is the chemicals were of analytical grade and used as received similar to indocyanine green, but superior to indocyanine without further purification. C6 cell line was purchased green in terms of stability. IR820 can be easily metabolized from the China Center for Type Culture Collection (Wuhan by the liver.24,25 Due to its good biosecurity, IR820 was University). The consumables of cell culture in this work were employed as the photothermal agent in this study.26,27 purchased from Beijing Dingguo Changsheng Biotechnology
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