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A metal-organic framework-based redox homeostasis disruptor selectively potentiate the cytotoxicity of dihydroartemisinin for cancer therapy

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Nano Research 2023年第5期16卷 7489-7495页

作者： Jiawen Fan Xinchen Liu Qishun Wang Huan Wang Hao Liu Deming Han Jinsong Ren School of Life Science and Technology Changchun University of Science and TechnologyChangchun 130022China State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of StomatologyJilin UniversityChangchun 130021China Department of Chemistry Tsinghua UniversityBeijing 100084China

Artemisinin and its derivatives have emerged as promising therapeutic agents for cancer therapy by endogenous iron-mediated generation of free ***,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 ***,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 *** 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 *** a result,the damaged antioxidant defense system of cancer cells reduces its effect on oxidative stress alleviation and strengthens the therapeutic efficacy of *** contrast,the low concentration of cellular glutathione in normal cells protects them from dihydroartemisinin-induced cytotoxicity by decelerating the drug *** 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.

关键词： metal-organic framework dihydroartemisinin selective cancer therapy redox homeostasis disruptor glutathione depletion

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