Key Laboratory of Materials Chemistry for Energy Conversion and Storage (HUST) of Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
J Mater Chem B. 2019 Jan 21;7(3):460-468. doi: 10.1039/c8tb03030h. Epub 2018 Dec 19.
The combination of chemotherapy and photodynamic therapy (PDT) using polymeric nanocarriers is effective for improving therapeutic efficiency against cancer. Yet, in most reported cases, due to the lack of synergistic mechanisms, chemotherapy and PDT work independently rather than synergistically-the functions of chemotherapeutic drugs and photosensitizers in nanocarriers are independent when they are delivered to cancer cells. Here, we demonstrate the construction of reactive oxygen species (ROS)-degradable nanoparticles (NPs) based on phenylboronic pinacol ester-conjugated dextran (PPE-Dex) through a membrane-extrusion emulsification approach for the co-delivery of anticancer drug (e.g., doxorubicin, Dox) and photosensitizer (e.g., chlorin e6, Ce6). When exposed to 655 nm laser irradiation, ROS generated by encapsulated Ce6 not only induced a significant PDT effect in cancer cells, but also triggered the rapid oxidization and degradation of PPE-Dex, resulting in the quick release and enhanced intra-nuclei accumulation of Dox. In vitro cytotoxicity and combination index (CI) assay indicated that the PPE-Dex NPs offered remarkable synergistic therapeutic effects of Dox and Ce6 against cancer cells under irradiation. Furthermore, the drug release profiles can be well regulated by changing the irradiation time to satisfy different demands in various treatment programs. Our results demonstrated that such ROS-degradable polymeric NPs with light-activated disassembly capability are promising carriers for synergistic photodynamic-chemo therapy in cancer therapy.
化疗与光动力疗法（PDT）联合使用聚合物纳米载体可有效提高癌症治疗效率。然而，在大多数已报道的案例中，由于缺乏协同机制，化疗和 PDT 通常是独立作用而不是协同作用-当化疗药物和光敏剂被递送到癌细胞时，它们在纳米载体中的功能是相互独立的。在这里，我们通过膜挤出乳化方法构建了基于苯硼酸频哪醇酯接枝葡聚糖（PPE-Dex）的活性氧（ROS）可降解纳米颗粒（NPs），用于共递送抗癌药物（例如阿霉素，Dox）和光敏剂（例如氯乙酮，Ce6）。当暴露于 655nm 激光照射时，封装的 Ce6 产生的 ROS 不仅在癌细胞中引起了显著的 PDT 效应，而且还引发了 PPE-Dex 的快速氧化和降解，导致 Dox 的快速释放和增强的核内积累。体外细胞毒性和组合指数（CI）测定表明，PPE-Dex NPs 在照射下对癌细胞具有显著的 Dox 和 Ce6 协同治疗效果。此外，通过改变照射时间可以很好地调节药物释放曲线，以满足各种治疗方案的不同需求。我们的结果表明，这种具有光激活解组装能力的 ROS 可降解聚合物 NPs 是癌症协同光动力化疗的有前途的载体。
