环境响应性纳米载体系统对产生多药耐药性的肿瘤进行药物与基因的同时递送治疗是生物医药领域的一大热点和难点，具有重大的研究意义，故创新性地设计、合成该类载体系统是一项十分必要且有意义的工作。本项目拟在课题申请人前期工作基础上，设计、合成多种有机分子，并利用双重静电相互作用构建多重环境响应性肽类树状大分子药物-SiRNA纳米共载系统。该载体系统有希望可在肿瘤细胞外pH值和溶酶体中酶的调控下发生两阶段解离，同时破解PEG较大体积阻碍细胞吞噬以及PEG胞外离去导致SiRNA提前释放的问题，快速有效地在胞内同时释放药物与SiRNA；通过适当的化学或生物学实验方法，对递送系统的表面形貌、聚集与解离行为、释放行为等进行研究，并进行体内外药效学及生物安全性评价，探究其在药物/SiRNA递送中的应用。

The design and preparation of expriment responsive nanosacle co-delivery system of anti-tumor drug and SiRNA have recently received tremendous attention in field of biomedicine. We plan to synthesis a variety of functional organic molucules and construct multiple environmental responsive co-delivery nanoscale system via dual electrostatic interactions based on our previous work. This brandnew sort of co-delivery system is hypothesized to be capable of twice disassembling under the stimuli of microenvironment of tumor, including the extrocellular pH and enzyme in lysosome. It has ability to resolve these two problems about the cellular uptake of PEGylated vehicle and the early release of SiRNA after the liberation of PEG moities in the same time. Due to the fantastic character, this particular kind of nanoscale carrier is capable of simultaneously releasing the anti-tumor drug and SiRNA within the tumor cell fast and efficiently. In this project, we plan to characteriz the size, behavior of assemble and disassamble, the release of drug and SiRNA of the co-delivery system. Moreover, the in vitro an in vivo anti-tumor efficacy and biosafety of this nanoscale delivery system will be extimated.