非病毒载体的高效转染，是实现基因有效治疗的重要前提。本项目采用体内稳定、靶细胞高效摄取、具有细胞核趋向性的纳米载体，通过亲水性多糖与疏水性脂链之间的二硫键化学链接，形成靶细胞内高谷胱甘肽浓度响应性新型糖脂载体基因给药系统。研究基因给药系统主动靶向修饰与体内有效分布、细胞高效摄取之间的相关性，探索基因给药系统的外壳卸载型二硫键修饰、pH响应组氨酸分子修饰，促进基因在细胞内的谷胱甘肽敏感释放及内涵体逃逸的机理。阐明基因给药系统的理化性质、空间结构与体内分布、细胞摄取、细胞内基因释放，及细胞核趋向性之间的相互关系。在基因给药系统生物稳定性、安全性研究的基础上，通过肿瘤模型细胞和肿瘤模型动物的基因转染与基因治疗研究，探明基因给药系统生物靶向、基因转染效率与基因治疗疗效之间的内在规律性，为非病毒载体的高效基因转染与基因治疗研究，提供新思路、新策略和新方法，丰富和发展非病毒载体基因治疗理论体系。

The high gene transfection of the non-viral gene delivery system is importance premise to realize the efficient gene therapy. In this project, we designed an in vivo stable nano carrier, which display excellent uptake ability by targeting cells and cellular nucelus import ability. Through the hydrophilic polysaccharides was conjugated with octadecylamine by disulfide linkage, a novel intracellular splendid glutathione-responsive glycolipid-like gene delivery vector should be formed. The relationship between the effective distribution in vivo, tumor targeting, excellent cellular-uptake and the active targeting modification of the vector will be studied. There are also explored the inherent law of the modification of the histidine and disulfide bonds of shell-sheddable micelles with the genes escaping from endosome and intracellular release. By the research of gene transfection on tumor model cell lines and tumor model animals, we investigated the relevance between biological targeting and gene transfer efficiency. As considered to be biological stabile and safe, we further expounded the inherent law of both in vitro and in vivo gene therapy. This study will provide new idea, strategy and approach for efficient gene transfection and tumor gene therapy of non-viral gene delivery system, and enlarge and develop the gene therapeutical theory of non-viral gene delivery system.