本项目针对目前靶向肿瘤起始细胞（TICs）药物递送系统中靶向效率低与胞内释药不完全的现状和集成诱导TICs凋亡分子机制展开研究。设计并合成嵌段共聚物PLA-SS-PEI和具有线粒体靶向功能药物TPP-DTX构建同时包载基因药物miRNA-31和化疗药物多西紫杉醇衍生物的集成靶向聚离子复合物胶束PP/mPPTR。采用药剂学、细胞生物学、分子生物学、肿瘤学等手段揭示聚离子复合物胶束入胞途径、胞内转运、胞内释药机制及诱导TICs凋亡分子机制，为TICs靶向药物递送系统的研究奠定基础和提供参考。

The aim of this project is to investigate the molecular mechanism of tumor imitating cell (TICs) induced apoptosis effect to resolve the problems associated with current TICs targeted drug delivery systems including the low efficiency of targeting and insufficient intracellular release of therapeutical agents. Poly (lactic acid) - disulfide linkage-polyethyleneimine (PLA-SS-PEI) block copolymer and mitochondria-targeted derivate triphenylphosphine-docetaxel (TPP-DTX) will be synthesized and used to construct the polyionic complex (PP/mPPTR), which is expected to have the capacity of targeting at hierarchical and efficient co-delivering TPP-DTX and micro RNA-31 (miR-31). The intracellular drug release behavior, the pathway of cellular uptake, the mechanism of endocytosis and intracellular trafficking of the PP/mPPTR will be studied comprehensively and systematically by applying the tools of pharmaceutics, cytobiology, molecular biology and oncology. The mechanism of our novel DDS to induce apoptosis in cancer cell will be investigated. The achievement of this project will promote the progress in the field of TICs targeted DDS.