Dynamic-Covalent Hydrogel with NIR-Triggered Drug Delivery for Localized Chemo-Photothermal Combination Therapy
Dynamic-Covalent Hydrogel with NIR-Triggered Drug Delivery for Localized Chemo-Photothermal Combination Therapy
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具有近红外触发药物递送功能的动态共价水凝胶用于局部化学光热联合治疗
DOI：
10.1021/acs.biomac.9b01290
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发表时间：
2020
影响因子：
6.2
通讯作者：
Fan Quli
中科院分区：
文献类型：
--
作者：
Sun Pengfei;Huang Ting;Wang Xiaoxiao;Wang Gaina;Liu Zhijia;Chen Guosong;Fan Quli
近红外（NIR）光响应性可注射水凝胶由于其微创给药和远程控制方式而成为最有前途的局部抗癌治疗药物递送系统之一。然而，目前报道的大多数近红外响应水凝胶通常是通过热敏聚合物和光热转化剂的物理混合来生成的。本研究设计了一种具有近红外光触发释药特性的新型动态共价水凝胶（GelPV-DOX-DBNP），用于肿瘤的化学光热联合治疗。该水凝胶通过苯并氧杂硼杂环戊烯（BOB）修饰的透明质酸（BOB-HA）和果糖基糖基共聚物（PolyFru）之间的特异性苯并氧杂硼杂环戊烯-碳水化合物相互作用而形成，其中光敏剂二萘嵌苯二酰亚胺两性离子聚合物（PDS）、还原剂抗坏血酸（Vc）、抗癌药物阿霉素（DOX）以及光热纳米颗粒（DB-NPs）同时被封装。在660 nm光照射下，所设计的水凝胶中的PDS和Vc都可以将氧转化为过氧化氢，这可以通过基于苯并氧杂硼杂环戊烯-碳水化合物相互作用的动态共价键的断裂使水凝胶降解，导致从GelPV-DOX-DBNP中NIR光活化释放DOX和DB-NP。此外，释放的DB-NP可以将915 nm的光辐射转化为热，使得GelPV-DOX-DBNP能够作为用于化疗和光热治疗（PTT）的NIR响应性药物递送平台。体内实验结果证明，与单独化疗或PTT相比，GelPV-DOX-DBNP对4 T1肿瘤模型小鼠表现出显著增强的化疗-光热协同治疗。本工作提出了一种新的策略，以构建近红外光响应水凝胶作为一种替代药物输送系统的抗癌应用。
Near-infrared (NIR) light-responsive, injectable hydrogels are among the most promising drug delivery systems for localized anticancer therapy owing to its minimally invasive administration and remote-controlled manner. However, most currently reported NIR-responsive hydrogels were usually generated through physical mixing of thermosensitive polymers and photothermal conversion agents. In this study, a novel type of dynamic-covalent hydrogel (GelPV-DOX-DBNP) with NIR light-triggered drug release behavior was rationally designed for chemo-photothermal combination treatment of tumors. Concretely, this NIR-responsive hydrogel was formed by specific benzoxaborole-carbohydrate interactions between benzoxaborole (BOB)-modified hyaluronic acid (BOB-HA) and fructose-based glycopolymer (PolyFru), where photosensitizer perylene diimide zwitterionic polymer (PDS), reductant ascorbic acid (Vc), anticancer drug doxorubicin (DOX) as well as photothermal nanoparticles (DB-NPs) were encapsulated, simultaneously. Upon 660 nm light irradiation, both PDS and Vc within the designed hydrogel can convert oxygen into hydrogen peroxide, which could make hydrogel be degraded through the breakage of dynamic covalent bonds based on benzoxaborole-carbohydrate interactions, leading to NIR light-activatable release of DOX and DB-NPs from GelPV-DOX-DBNP. Furthermore, the released DB-NPs can convert 915 nm light irradiation into heat, enabling the application of GelPV-DOX-DBNP as a NIR-responsive drug delivery platform for both chemotherapy and photothermal therapy (PTT). In vivo results prove that GelPV-DOX-DBNP exhibited a markedly enhanced chemo-photothermal synergistic therapy for 4T1 tumor model mice, compared to chemotherapy alone or PTT. This work presents a new strategy to construct NIR light-responsive hydrogel as one alternative drug delivery system for anticancer applications.