动态共价水凝胶与近红外触发药物递送，用于局部化学-光热联合疗法。,Biomacromolecules

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动态共价水凝胶与近红外触发药物递送，用于局部化学-光热联合疗法。
Biomacromolecules ( IF 5.5 ) Pub Date : 2019-12-12 , DOI: 10.1021/acs.biomac.9b01290
Pengfei Sun ₁ , Ting Huang ₁ , Xiaoxiao Wang ₁ , Gaina Wang ₁ , Zhijia Liu _{2,

3} , Guosong Chen ₄ , Quli Fan ₁

Affiliation

由于其微创管理和远程控制方式，近红外（NIR）光反应性，可注射水凝胶是局部抗癌治疗最有希望的药物输送系统之一。但是，目前大多数报道的对NIR敏感的水凝胶通常是通过热敏聚合物和光热转化剂的物理混合产生的。在这项研究中，合理地设计了一种新型的具有NIR光触发药物释放行为的动态共价水凝胶（GelPV-DOX-DBNP），用于肿瘤的化学-光热联合治疗。具体地说，这种NIR响应水凝胶是由苯并xaborole（BOB）修饰的透明质酸（BOB-HA）与果糖基糖聚合物（PolyFru）之间的特定苯并xaborole-碳水化合物相互作用形成的，其中分别封装了光敏剂per二酰亚胺两性离子聚合物（PDS），还原剂抗坏血酸（Vc），抗癌药阿霉素（DOX）以及光热纳米颗粒（DB-NP）。在660 nm的光照射下，设计的水凝胶中的PDS和Vc都可以将氧气转化为过氧化氢，这可以使水凝胶通过基于苯并氧杂硼酸酯-碳水化合物相互作用的动态共价键的断裂而降解，从而导致近红外光可活化的DOX释放和来自GelPV-DOX-DBNP的DB-NP。此外，释放的DB-NP可以将915 nm的光辐照转化为热量，从而使GelPV-DOX-DBNP可以作为化学疗法和光热疗法（PTT）的近红外响应药物递送平台。体内结果证明，与单独化疗或PTT相比，GelPV-DOX-DBNP对4T1肿瘤模型小鼠表现出显着增强的化学-光热协同治疗。这项工作提出了一种新的策略来构建近红外光响应水凝胶，作为一种用于抗癌应用的替代药物递送系统。

"点击查看英文标题和摘要"

Dynamic-Covalent Hydrogel with NIR-Triggered Drug Delivery for Localized Chemo-Photothermal Combination Therapy.

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.

更新日期：2019-12-13

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