HER2抗体介导的pH敏感光交联聚合物胶束递药系统的构建及抗肿瘤研究

项目名称： HER2抗体介导的pH敏感光交联聚合物胶束递药系统的构建及抗肿瘤研究

项目编号： No.81202473

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 程亮

作者单位： 苏州大学

项目金额： 23万元

中文摘要： 针对现有胶束存在体内不够稳定和/或在靶细胞内释药缓慢的问题，本项目旨在构建集体循环稳定、肿瘤靶向识别及细胞内涵体pH响应释药等多功能的胶束递药系统，以期提高胶束的肿瘤靶向效率，同时实现抗癌药物在靶细胞内的快速释放。该胶束由PEG-PAC-PTMBPEC和Trastuzumab-PEG-PTMBPEC在水中自组装后光照交联制备得到，其中PAC为含可光交联丙烯酸基团的聚碳酸酯、PTMBPEC为侧链含酸敏感可降解缩醛基团的聚碳酸酯，Trastuzumab为靶向HER2抗体。该智能胶束具有以下特点：（1）通过交联，胶束具有高度的稳定性，可在体内滞留更长时间，增加其被动靶向效率；（2）经单抗修饰的胶束可被靶细胞特异性内吞；（3）胶束在细胞内涵体酸性环境中快速水解并迅速释放药物。本项目设计的抗体介导的pH敏感交联胶束有望实现乳腺癌的高效靶向药物递送，同时为智能递送系统的设计提供理论及实验依据。

中文关键词： 聚合物载体；肿瘤靶向；pH敏感；高稳定；药物递送

英文摘要： To solve the problems that existing micelles are not stable enough in the body and/or release slowly in targeted cells, we aim to build a multifunctional polymer micelle drug delivery system, with functions of stability in systemic circulation, active tumor targeting and pH-responsive intracellular release of drug, in order to enhance tumor targeting efficiency of the micelles and achieve a rapid release of anti-cancer drugs in targeted cells. The micelles were prepared by PEG-PAC-PTMBPEC and Trastuzumab-PEG-PTMBPE self-assembled in the water and then cross-linked by UV irradiation. The PAC is polycarbonate which contains photo-cross-linkable acrylic groups and the PTMBPEC is polycarbonate whose side chain contains degradable acid-sensitive acetal groups. Trastuzumab is HER2 targeting antibody. This smart micelles have following characteristics: (1) by cross-linking, the micelles have a high degree of stability so they can stay longer in the body circulation, and thus increase their passive targeting efficiency; (2) modified by the monoclonal antibody, the micelles can be specifically endocytosed by targeted cells; (3) the micelles can be hydrolysed rapidly in the acidic environment of the endosomes and quickly release the drug. The antibody-mediated pH-sensitive cross-linked micelles are expected to achieve eff

英文关键词： Polymeric carrier；Tumor targeting；pH sensitive；High stability；Drug delivery