项目针对脂质体抗癌药物传递系统面临的无隐形功能、稳定性差、无细胞器靶向性等主要问题，设计构建一类基于改性磷脂的新型多功能药物传递系统。以生物相容性好的二硬脂酰基磷脂酰乙醇胺（DSPE）与含巯基化合物构建具有可二硫键交联和细胞内环境敏感的改性磷脂；DSPE、线粒体靶向肽和马来酸酐共同构建具有电荷翻转和线粒体靶向功能的改性磷脂。以上述改性磷脂、天然磷脂和胆固醇，通过自组装，构建同时具有隐形、高稳定性、肿瘤微环境敏感、线粒体靶向的多功能脂质体药物传递系统。利用二硫键交联结构、血液循环中脂质体呈负电荷、在肿瘤弱酸性环境脂质体电荷翻转为正电荷、细胞内高浓度谷胱甘肽破坏二硫键以及(KLAKLAK)2多肽等多种因素共同作用，克服脂质体抗癌药物传递系统面临的诸多问题，实现高效抗癌效果。通过本项目的实施，将获得一类新型的多功能脂质体纳米药物传递系统，为研发具有临床应用前景的脂质体抗癌药物传递系统奠定基础。

The lack of stealth, poor stability and non-targeting to organelle are the main problems that liposome-based antitumor drug delivery systems faced. In this project, a novel multifunctional drug delivery system (DDS) based on modified phospholipids was fabricated. Cross-linkable phospholipids were synthesized based on the distearoylphosphatidylethanolamine (DSPE) and sulphydryl compounds. Charge reversal and mitochondrion targeting phospholipids were synthesized based on DSPE, mitochondrion targeting peptide and maleic hydride. The modified phospholipids, natural phospholipids and cholesterol were self-assembled to multifunctional liposomal DDS. This liposomal DDS possessed stealth, good stability, tumor microenvironmental sensitivity and mitochondrion targeting. These integrated functions were expected to resolve the problems that liposomal DDS faced and enhance the antitumor efficacy. The implantation of this project would achieve a novel multifunctional liposomal DDS. It would provide a new strategy for the design and construction of antitumor DDS to promote the development of chemotherapy for cancer.