基于超支化聚磷酸酯非病毒基因载体的构建及应用研究

项目名称： 基于超支化聚磷酸酯非病毒基因载体的构建及应用研究

项目编号： No.21204048

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 高分子科学

项目作者： 庞燕

作者单位： 上海交通大学

项目金额： 25万元

中文摘要： 目前，设计合成高效低毒的非病毒基因载体是构建高效安全基因输送体系以及推动基因治疗临床应用的关键科学问题之一。研究结果表明在实现高转染效率的同时通常面临着高毒性问题，这严重阻碍了基因治疗临床应用的进程。本项目拟在课题组原有工作基础上，设计合成一类含磷超支化聚合物的高效低毒非病毒基因载体。采用自缩合开环聚合，制备多种结构可控、生物相容、生物可降解的阳离子型超支化聚磷酸酯，突破传统基因载体材料在安全性方面的局限性。通过控制阳离子型超支化聚磷酸酯的分子结构，具体阐明拓扑结构和电荷分布与DNA复合能力之间的相互关系。以阳离子型超支化聚磷酸酯为非病毒基因载体，可同时实现载体在细胞外与DNA的有效结合以及细胞内因载体快速降解而迅速释放DNA，从而达到DNA的低毒输送和高效转染。新型阳离子型超支化聚磷酸酯载体材料的发展为基因治疗的临床应用提供了新契机。

中文关键词： 癌症；基因治疗；药物治疗；超支化聚合物；

英文摘要： Currently, design and synthesis of a highly efficient and low cytotoxicity nonviral gene delivery vehicle is one of the key points for the construction of highly efficient and safe gene delivery systems as well as the development of clinical application of gene therapy. However, the previously reported gene delivery vectors always involved with cytotoxicity problems impeding the development of clinical application of gene therapy. In this project, we present a highly efficient and low cytotoxicity nonviral gene carrier material based on phosphonium-containing hyperbranched polymers. Various kinds of structure controllable, biocompatible and biodegradable cationic hyperbranched polyphosphates can be prepared by using self-condensing ring-opening polymerization. The relationship of structure of cationic hyperbranched polyphosphates and the complex ability with DNA can be illustrated via adjusting the topology structure and charge distribution of the polymers. Cationic hyperbranched polyphosphates and DNA can form stable complexes, while the loaded DNA can be rapidly released because of the fast degradation of carrier in cells. Cationic hyperbranched polyphosphates can be used to realize the low cytotoxicity and highly efficient gene delivery, which provides an opportunity for the development of clinical applicatio

英文关键词： Cancer；gene therapy；drug therapy；hyperbranched polymer；