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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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Abstract

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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Acknowledgements

This work was supported by the Program of Science and Technology Development Plan of Jilin Province of China (No. 20200201099JC), and the National Natural Science Foundation of China (Nos. 21871249 and 22105197).

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Authors and Affiliations

  1. School of Life Science and Technology, Changchun University of Science and Technology, Changchun, 130022, China

    Jiawen Fan & Deming Han

  2. State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Huan Wang, Hao Liu & Jinsong Ren

  3. Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, China

    Xinchen Liu

  4. Department of Chemistry, Tsinghua University, Beijing, 100084, China

    Qishun Wang

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  1. Jiawen Fan
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  2. Xinchen Liu
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  3. Qishun Wang
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  4. Huan Wang
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  5. Hao Liu
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Correspondence to Huan Wang, Deming Han or Jinsong Ren.

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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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Fan, J., Liu, X., Wang, Q. et al. A metal-organic framework-based redox homeostasis disruptor selectively potentiate the cytotoxicity of dihydroartemisinin for cancer therapy. Nano Res. 16, 7489–7495 (2023). https://doi.org/10.1007/s12274-023-5385-8

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  • DOI: https://doi.org/10.1007/s12274-023-5385-8

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