肿瘤部位的靶向敏感释放一直是化疗药物靶向递送中存在的重要问题。本项目拟通过肿瘤内环境响应设计，将脂质材料进行合成改造，通过二硫键链接脂质分子和具有P-gp抑制作用的槲皮素，以此为基础制备肿瘤细胞内高谷胱甘肽浓度响应性与P-gp抑制作用的抗肿瘤靶向脂质纳米给药系统。阐明其理化性质、空间结构与细胞摄取及体内外还原敏感释药能力的相关关系。阐明给药系统在高还原物质浓度肿瘤细胞内的敏感释放与疗效的关系，以及功能性脂质纳米载体对耐药肿瘤细胞中P-gp过表达的抑制作用与相关机制。通过肿瘤模型动物的药效研究，考察功能性脂质纳米给药系统的生物靶向、耐药抑制、治疗疗效与生物安全性，为功能性脂质纳米给药系统的治疗研究提供新思路、新策略，丰富和发展环境响应性纳米给药系统治疗理论体系。

Target and sensitive release of drug to the tumor site have always been the problems of cancer chemotherapy. In this study, we plan to design a new lipid material based on responsive to tumor internal environment, which is conjugated lipid molecular with Quercetin of P-gp inhibitory property by disulfide bond. And further prepare antitumor targeting lipid nanoparticle drug delivery system that responsive to high glutathione concentration in cancer cells with P-gp inhibition. The relationship between physicochemical properties, spatial structure, and cell uptake, release susceptibility in vitro and in vivo will be studied. Expounding the relationship between responsive release and therapeutic effect of the drug delivery system in the tumor cells with high concentration of reducing substances. Discuss the relationship of inhibition effect of the functional lipid nanoparticle on the P-gp overexpression in the drug-resistant tumor cells and the mechanism. Exploring the biological targeting, drug resistance, therapeutic efficacy and biosafety of functional lipid nanoparticle drug delivery system by studying the pharmacodynamics of tumor model animals, and to provide new ideas and strategy for the treatment of functional lipid nanoparticle drug delivery system, to enrich and develop the environmental-responsive nanoparticle drug delivery system for the treatment of theoretical systems.