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Targeting ferroptosis by poly(acrylic) acid coated Mn3O4 nanoparticles alleviates acute liver injury

Author

Listed:
  • Xinyi Shan

    (Huazhong Agricultural University
    Hubei Hongshan Laboratory)

  • Jiahuan Li

    (Huazhong Agricultural University
    Hubei Hongshan Laboratory)

  • Jiahao Liu

    (Hubei Hongshan Laboratory
    Huazhong Agricultural University
    Tarim University)

  • Baoli Feng

    (Huazhong Agricultural University
    Hubei Hongshan Laboratory)

  • Ting Zhang

    (Huazhong Agricultural University
    Hubei Hongshan Laboratory)

  • Qian Liu

    (Huazhong Agricultural University
    Hubei Hongshan Laboratory)

  • Huixin Ma

    (Hubei Hongshan Laboratory
    Huazhong Agricultural University)

  • Honghong Wu

    (Hubei Hongshan Laboratory
    Huazhong Agricultural University
    Huazhong Agricultural University
    Chinese Academy of Agricultural Sciences)

  • Hao Wu

    (Huazhong Agricultural University
    Hubei Hongshan Laboratory)

Abstract

Ferroptosis, a newly characterized form of regulated cell death, is induced by excessive accumulation of lipid peroxidation catalyzed by intracellular bioactive iron. Increasing evidence has suggested that ferroptosis is involved in the pathogenesis of several human diseases, including acute liver injury. Targeted inhibition of ferroptosis holds great promise for the clinical treatment of these diseases. Herein, we report a simple and one-pot synthesis of ultrasmall poly(acrylic) acid coated Mn3O4 nanoparticles (PAA@Mn3O4-NPs, PMO), which perform multiple antioxidant enzyme-mimicking activities and can scavenge broad-spectrum reactive oxygen species. PMO could potently suppress ferroptosis. Mechanistically, after being absorbed mainly through macropinocytosis, PMO are largely enriched in lysosomes, where PMO detoxify ROS, inhibit ferritinophagy-mediated iron mobilization and preserve mTOR activation, which collectively confer the prominent inhibition of ferroptosis. Additionally, PMO injection potently counteracts lipid peroxidation and alleviates acetaminophen- and ischaemia/reperfusion-induced acute liver injury in mice. Collectively, our results reveal that biocompatible PMO act as potent ferroptosis inhibitors through multifaceted mechanisms, which ensures that PMO have great translational potential for the clinical treatment of ferroptosis-related acute liver injury.

Suggested Citation

  • Xinyi Shan & Jiahuan Li & Jiahao Liu & Baoli Feng & Ting Zhang & Qian Liu & Huixin Ma & Honghong Wu & Hao Wu, 2023. "Targeting ferroptosis by poly(acrylic) acid coated Mn3O4 nanoparticles alleviates acute liver injury," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43308-w
    DOI: 10.1038/s41467-023-43308-w
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    References listed on IDEAS

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