肿瘤细胞亚细胞结构靶向和释放的药物递释系统，是实施药物高效安全治疗的关键。本项目选择糖脂嫁接物为载体母核，以三苯基膦修饰，低分子壳聚糖及核定位信号肽、适配体修饰，分别靶向肿瘤细胞线粒体与细胞核，采用二硫键、酯键、磷酸二酯键链接壳聚糖和硬脂酸，实现线粒体、细胞核内药物敏感释放，构建以线粒体、细胞核为代表的亚细胞结构靶向药物递释系统。研究不同类别、不同比例靶向基团修饰与靶向效率之间的相关性。通过测定亚细胞结构的pH值及GSH与脂酶、核酸酶浓度，研究病理生理学参数与内环境敏感释放之间的分子机制。阐明药物递释系统的分子设计与亚细胞结构靶向、释放之间的内在联系。通过模型细胞和模型动物的动态分布、动态释放及药效学研究，探明药物递释系统的亚细胞结构靶向、释放，与细胞药效、体内药效之间的内在规律性，为药物递释系统的高效安全治疗，提供新思路、新策略和新方法，丰富和发展肿瘤治疗理论体系。

The design of drug delivery system about tumor cells’ subcellular structure targeting and drug releasing, has increasingly become the key to highly effective and safe treatment. In this project, glycolipid conjugate is chosen as the nanocarrier core, which is modified with triphenylphosphine (CTPP), or chitosan in low molecular weight, nuclear localization signal (NLS) and aptamer (Apt), to target mitochondria and nucleus in tumor cells, respectively. In the meantime, disulfide bond, ester bond and phosphate diester bond are used as the linkage between chistosan and stearic acid, which can realize fast drug releasing in mitochondria and nucleus, respectively. The relationship between the targeting group modified with different species and conjugation ratios, and the targeting efficiency will be studied. By determining the pH values, GSH levels and concentration of esterase and nucleic acid enzymes in subcellular structure, we will focus on the molecular mechanism between pathophysiological parameters and responsive release at the internal environment of subcellular structures. We aim to illustrate the relevance between the design of drug delivery system and the subcellular structure targeting and drug releasing. By the research of dynamic distribution, dynamic release and pharmacodynamics on tumor cell model and tumor animal model, we further hope to expound the inherent law between subcellular structure targeting and drug releasing of drug delivery system and the therapeutic efficacy in vitro and in vivo. This study will provide new idea, strategy and approach for tumor therapy based on efficient and safe drug delivery system, and then enlarge and expand the tumor therapeutical theory.