核壳结构超支化共轭聚合物的双光子荧光增强及光动力治疗

项目名称： 核壳结构超支化共轭聚合物的双光子荧光增强及光动力治疗

项目编号： No.51473093

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 朱新远

作者单位： 上海交通大学

项目金额： 90万元

中文摘要： 构建双光子荧光增强的聚合物纳米材料是发展光动力治疗的重要途径。现有的双光子纳米材料存在荧光强度低、水溶性差、光稳定性弱及非特异性靶向等问题，本项目拟利用高度支化空间拓扑结构阻断疏水分子相互聚集，研制新型双光子荧光增强的核壳结构超支化共轭聚合物，并用于肿瘤光动力治疗。采用交叉偶联聚合反应技术，制备结构可控的超支化共轭聚合物，在此基础上合成温度响应性超支化聚合物修饰的超支化共轭聚合物。借助高度支化聚合物特有的单分子胶束的多胶束聚集自组装，获得双光子荧光增强的功能性聚合物纳米胶束。系统阐明超支化共轭聚合物的支化结构和自组装行为对双光子荧光性能的影响。将抗肿瘤光敏剂接枝到核壳结构超支化共轭聚合物表面，利用红外光的组织穿透性和热效应触发并控制光动力治疗，实现对肿瘤细胞的特异性识别和有效抑制。通过上述系统研究，将有助于丰富双光子荧光材料作为药物载体的尝试，为肿瘤光动力治疗提供新途径。

中文关键词： 生物医用高分子；药物载体；纳米材料；刺激响应性；光动力治疗

英文摘要： Design and construction of the polymeric nanomaterials with two-photo emission enhancement properties are currently one of the important strategies for the photodynamic therapy. In the current stage, two-photo nanomaterials suffer from low two-photo emission properties, poor water-solubility, weak photostability and nonspecific targeting. To overcome these shortcomings, a novel kind of stimuli-responsive hyperbranched conjugated polymer with core-shell structure and two-photo emission enhancement properties will be developed in this project for photodynamic therapy by utilization of the steric hindrance of highly branched polymers to prevent from the aggregation of hydrophobic moieties. Firstly, hyperbranched conjugated polymers with controlled branching structure will be synthesized through cross-coupling polymerization, and then the hyperbranched conjugated polymers with core-shell structure will be obtained by the surface modification with flexible thermo-responsive hyperbranched polymers. Such hyperbranched polymers with a hyperbranched conjugated core and many flexible hyperbranched arms can form the unimolecular micelles in good solvents. Base on the unique self-assembly mechanism of highly branched polymers from unimolecular micelles to multi-micelle aggregates in an aqueous solution, the polymeric micelles with two-photo emission enhancement properties can be readily obtained. The relationship between two-photo emission properties and polymeric structures including the branched structure and self-assembled behavior of hyperbranched conjugated polymers will be investigated systematically. Finally, the photodynamic therapy will be carried out after the surface grafting of anti-cancer photo-sensitizer onto hyperbranched conjugated copolymers with core-shell structure. Benefiting from the thick tissue penetration depth and the fast heating effect of near infrared, the photodynamic therapy of hyperbranched conjugated copolymers with anti-cancer photo-sensitizer will be initiated and controlled through the photo-responsive properties. Consequently, the inhibition of tumor cells will be realized by the cooperative action between hyperbranched conjugated copolymers and anti-cancer photo-sensitizer, which will be verified by in vitro and in vivo evaluations. If this project works, it is no doubt that the two-photo emission nanomaterials can be used as drug carriers for promoting the development of tumor therapy.

英文关键词： Biomacromolecules;Drug carrier;Nanomaterials;Stimuli-responsive;Photodynamic therapy