细胞穿膜肽-聚合物偶联物的合成、组装与载药机制研究

项目名称： 细胞穿膜肽-聚合物偶联物的合成、组装与载药机制研究

项目编号： No.21504044

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 张强

作者单位： 南京理工大学

项目金额： 21万元

中文摘要： 细胞穿膜肽是一类具有优异的细胞膜穿透能力的短肽，在病毒对细胞的入侵以及生物活性大分子的体内转运等生命过程中发挥着重要作用。针对穿膜肽的稳定性及细胞特异性相对较差的特点，本项目开展穿膜肽-聚合物偶联物的结构设计与分子合成，系统研究偶联物的组装行为，并探索偶联物及其组装体的载药和跨膜传递机制。在设计制备出特定位点修饰的穿膜肽大分子引发剂的基础上，利用单电子转移活性自由基聚合，高效地从穿膜肽主链原位接枝一系列界定良好的具有可控分子量、窄分子量分布和多嵌段结构的聚合物，并通过功能性单体的选择赋予偶联物环境响应特性和对特定蛋白的靶向识别能力。进一步研究偶联物在水中的自组装行为，系统分析穿膜肽和聚合物的结构、组成以及外界环境因素对其自组装行为的影响，并初步探索偶联物及其组装体的载药行为和相关的细胞摄取机制。本项目可为穿膜肽-聚合物偶联物的合成、组装及载药传递机制的研究提供思路和理论支撑。

中文关键词： 细胞穿膜肽；含糖聚合物；活性自由基聚合；自组装；纳米药物

英文摘要： Cell-penetrating peptides (CPP) are short peptides with outstanding ability to translocate the plasma membrane and they play vital roles in many critical biological processes, such as those involved in the invasion of viruses to cells and in vivo delivery of many biomacromolecules. In order to improve the stability of CPP in vivo as well as the ability to target special cells, we carry out research on the design and synthesis of CPP-polymer conjugates. The self-assembly behaviour, drug delivery ability and cell-penetrating mechanism of CPP-polymer conjugates and relative assemblies were also discussed. CPP macroinitiators were first synthesized via chemical modification of certain functional groups and well-defined polymers with controlled molecular weight (MW), narrow MW distribution and multiblock structures were then in-situ grafted from CPP by single electron transfer living radical polymerization (SET-LRP) efficiently. Through particular selection of functional monomers, the synthesized CPP-polymer conjugates could have environmental responsive property and recognition behaviour with special proteins. Following that the effect of the structure and composition of CPP and polymer as well as the environmental factors on the self-assembly behaviour of the conjugates was discussed. The drug delivery ability and cellular uptake mechanism of the CPP-polymer conjugates and relative assemblies were further explored. It’s proposed that this research will be able to develop novel strategies in the synthesis of CPP-polymer conjugates and promote the research on relative self-assembly and cell-penetrating mechanism.

英文关键词： Cell-penetrating peptide;Glycopolymer;Living radical polymerization;Self-assembly;Nanomedicine