A metal-organic framework-based redox homeostasis disruptor selectively potentiate the cytotoxicity of dihydroartemisinin for cancer therapy
作者机构：School of Life Science and TechnologyChangchun University of Science and TechnologyChangchun 130022China State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical BiologyChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Jilin Provincial Key Laboratory of Tooth Development and Bone RemodelingHospital of StomatologyJilin UniversityChangchun 130021China Department of ChemistryTsinghua UniversityBeijing 100084China
出 版 物：《Nano Research》 (纳米研究（英文版）)
年 卷 期：2023年第16卷第5期
页 面：7489-7495页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 0703[理学-化学] 10[医学]
基 金：the Program of Science and Technology Development Plan of Jilin Province of China(No.20200201099JC) the National Natural Science Foundation of China(Nos.21871249 and 22105197).
主 题：metal-organic framework dihydroartemisinin selective cancer therapy redox homeostasis disruptor glutathione depletion
摘 要：Artemisinin and its derivatives have emerged as promising therapeutic agents for cancer therapy by endogenous iron-mediated generation of free radicals.However,the enhanced antioxidant defense systems in cancer cells provide them with resistance to oxidative damage,greatly antagonizing the therapeutic efficacy that relies on inducing oxidative stress.Herein,a metal-organic framework(MOF)-based nanoplatform(CMD)is constructed to disrupt the cellular redox homeostasis and selectively potentiate the cytotoxicity of dihydroartemisinin for cancer therapy.In cancer cells,the copper(II)sites in the MOF nanocarrier of CMD can efficiently weaken the cellular antioxidant capacity by depleting the overexpressed glutathione,simultaneously leading to the decomposition of the framework structure and the release of the encapsulated dihydroartemisinin.As a result,the damaged antioxidant defense system of cancer cells reduces its effect on oxidative stress alleviation and strengthens the therapeutic efficacy of dihydroartemisinin.On contrast,the low concentration of cellular glutathione in normal cells protects them from dihydroartemisinin-induced cytotoxicity by decelerating the drug release.In vivo results demonstrate that CMD could completely suppress the tumor growth in mice and show no evidence of toxicity,providing an effective strategy for the practical usage of dihydroartemisinin in cancer therapy.
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