主链含铂光刺激响应高分子纳米胶束的药物控释研究

The potential application of backbone-type photo-responsive block copolymer micelles as controlled drug delivery systems for cancer treatment is limited by the toxicity of photochromic groups, range of photo-responsive wavelengths, anti-cancer activity evaluation and structural functions. There is correspondingly a clear incentive to develop new photo-responsive copolymer micelles system for tunable, controllable, more effective and safer cancer therapy. Anti-cancer prodrugs, photo-activated platinum (IV) complexes, are creatively used as photo-responsive groups and inserted repeatedly into the hydrophobic main chain to prepare platinum-containing backbone-type photo-responsive block copolymer micelles. Firstly, these platinum-containing photo-responsive polymer micelles themselves are polymeric photo-chemotherapy systems, in which active platinum (II) anti-cancer drugs would be released after UV to NIR light-induced fast degradation of the polymer backbones. Meanwhile, they are also drug carriers which can load and photo-control release other anticancer drugs such as chemotherapeutics or photosensitizers easily for different types of combination therapies, resulting in enhanced anticancer efficacy. Taking advantages of wide responsive wavelengths coverage and different types of combination therapies of the platinum-containing photo-responsive polymer micelles, the effectiveness and mechanisms of controlled drug release and individual cancer treatment are in-depth studied, providing theoretical guidance and experimental basis for the design of other high-level photo-responsive polymer micelle systems.

主链光刺激响应高分子纳米胶束作为药物控释载体在癌症治疗中受到光调控波长窄、结构功能单一、光敏基团及光反应产物毒性不明确以及细胞动物研究不够深入等问题的限制，开发可调、可控、高效、低毒的新型主链光刺激响应高分子纳米胶束具有非常重要的意义。本项目创新性地将抗癌“前药”,四价光敏铂化合物,作为光刺激响应基团并重复地引入到高分子疏水主链中，形成了一类从紫外光到近红外光刺激响应的新型主链含铂光刺激响应高分子纳米胶束。该体系本身即为高分子光化疗体系，在光刺激下可以发生胶束主链响应性的崩解并光还原释放活性二价铂药；同时其又是控释载体，可以方便地担载和光控释其它抗癌药物如化疗试剂或光敏剂等实现不同方式的联合治疗，提高抗癌效果。充分利用该体系光刺激响应波长、联合治疗方式可调的优势，深入研究其药物控制释放和癌症个体化治疗的效果和机理，为更高水平的光刺激响应高分子纳米胶束体系设计提供理论指导和试验依据。

主链光刺激响应高分子纳米胶束作为药物控释载体在癌症治疗中受到光调控波长窄、结构功能单一、光敏基团及光反应产物毒性不明确以及细胞动物研究不够深入等问题的限制，开发可调、可控、高效、低毒的新型主链光刺激响应高分子纳米胶束具有非常重要的意义。本项目创新性地将抗癌“前药”,四价光敏铂化合物,作为光刺激响应基团并重复地引入到高分子疏水主链中，形成了一类从紫外光到近红外光刺激响应的新型主链含铂光刺激响应高分子纳米胶束。该体系本身即为高分子光化疗体系，在光刺激下可以发生胶束主链响应性的崩解并光还原释放活性二价铂药；同时其又是控释载体，可以方便地担载和光控释其它抗癌药物如化疗试剂或光敏剂等实现不同方式的联合治疗，提高抗癌效果。充分利用该体系光刺激响应波长、联合治疗方式可调的优势，深入研究其药物控制释放和癌症个体化治疗的效果和机理，为更高水平的光刺激响应高分子纳米胶束体系设计提供理论指导和试验依据。