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MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload

Author

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  • Weier Bao

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Ming Liu

    (University of Chinese Academy of Sciences)

  • Jiaqi Meng

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Siyuan Liu

    (University of Chinese Academy of Sciences)

  • Shuang Wang

    (Chinese Academy of Sciences)

  • Rongrong Jia

    (Shanghai Jiao Tong University School of Medicine)

  • Yugang Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Guanghui Ma

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Wei Wei

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhiyuan Tian

    (University of Chinese Academy of Sciences)

Abstract

Targeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (•OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.

Suggested Citation

  • Weier Bao & Ming Liu & Jiaqi Meng & Siyuan Liu & Shuang Wang & Rongrong Jia & Yugang Wang & Guanghui Ma & Wei Wei & Zhiyuan Tian, 2021. "MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26655-4
    DOI: 10.1038/s41467-021-26655-4
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    Cited by:

    1. Ying Huang & Geng Qin & TingTing Cui & Chuanqi Zhao & Jinsong Ren & Xiaogang Qu, 2023. "A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Gang He & Yashi Li & Muhammad Rizwan Younis & Lian-Hua Fu & Ting He & Shan Lei & Jing Lin & Peng Huang, 2022. "Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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