肿瘤细胞内高浓度的谷胱甘肽（GSH）是导致铂类药物耐药的重要原因。针对GSH调控这一关键问题，近年来，铂类药物与纳米技术相结的治疗策略取得了极大进展，但由于纳米体系合成组装过程繁琐、载药率低以及载体毒性等问题限制了其进一步应用。鉴于此，本项目以四价铂前药和Fe3+作为基本单元构建了“carrier-free”形式的Fe-Pt金属有机框架（MOF）纳米级联反应体系，通过降低GSH含量、化疗与化学动力学治疗（CDT）联合治疗解决铂类药物的耐药问题。本项目将在研究该纳米体系理化性质的基础上，以顺铂耐药型肿瘤细胞A549cisR、A2780cisR为模型，评价该纳米体系克服肿瘤耐药的效果。建立顺铂耐药细胞A549cisR的荷瘤鼠模型，在动物水平上研究该体系抗肿瘤效果，并进一步探讨作其用机制。该项目的研究成果有望为克服顺铂耐药性提供新的研究思路。

High level of intracellular glutathione (GSH) is one of the major causes for the resistance of platinum-based drugs in cancer therapy. Recently, to reduce the GSH level, a series of nano-therapeutic strategies have been developed for combination therapy with platinum-based drugs. Although great progress has been made in this filed, their subsequent application has been limited by complicated synthetic or assembling process, low drug loading ratio or toxicity of carriers. Therefore, it is urgently to explore a novel combinational therapeutic strategy basing on reducing GSH to overcome the resistance of platinum drug. To solve these problems, herein, we design and construct a “carrier-free” nano-cascade catalytic system basing on Fe-Pt metal organic framework (Fe-Pt nMOF) to regulate the concentration of GSH and to achieve a combination of chemo- and chemodanymic therapy. Firstly, the physical and chemical properties of Fe-Pt nMOF system will be studied, followed by in vitro cytotoxicity tests in both cisplatin-sensitive and –resistant cancer cell lines. Then, the effect on tumor growth suppression will be studied on the tumor-bearing mice in vivo. These results will provide new ideas to combat cisplatin-resistance in cancer therapy.