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Chiral metal-organic frameworks incorporating nanozymes as neuroinflammation inhibitors for managing Parkinson’s disease

Author

Listed:
  • Wei Jiang

    (the Second Affiliated Hospital of Zhengzhou University
    Zhengzhou University)

  • Qing Li

    (the Second Affiliated Hospital of Zhengzhou University)

  • Ruofei Zhang

    (Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Jianru Li

    (Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Qianyu Lin

    (the Second Affiliated Hospital of Zhengzhou University)

  • Jingyun Li

    (Zhengzhou University
    Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Xinyao Zhou

    (University of Pennsylvania)

  • Xiyun Yan

    (Zhengzhou University
    Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Kelong Fan

    (Zhengzhou University
    Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

Abstract

Nanomedicine-based anti-neuroinflammation strategy has become a promising dawn of Parkinson’s disease (PD) treatment. However, there are significant gaps in our understanding of the therapeutic mechanisms of antioxidant nanomedicines concerning the pathways traversing the blood-brain barrier (BBB) and subsequent inflammation mitigation. Here, we report nanozyme-integrated metal-organic frameworks with excellent antioxidant activity and chiral-dependent BBB transendocytosis as anti-neuroinflammatory agents for the treatment of PD. These chiral nanozymes are synthesized by embedding ultra-small platinum nanozymes (Ptzymes) into L-chiral and D-chiral imidazolate zeolite frameworks (Ptzyme@L-ZIF and Ptzyme@D-ZIF). Compared to Ptzyme@L-ZIF, Ptzyme@D-ZIF shows higher accumulation in the brains of male PD mouse models due to longer plasma residence time and more pathways to traverse BBB, including clathrin-mediated and caveolae-mediated endocytosis. These factors contribute to the superior therapeutic efficacy of Ptzyme@D-ZIF in reducing behavioral disorders and pathological changes. Bioinformatics and biochemical analyses suggest that Ptzyme@D-ZIF inhibits neuroinflammation-induced apoptosis and ferroptosis in damaged neurons. The research uncovers the biodistribution, metabolic variances, and therapeutic outcomes of nanozymes-integrated chiral ZIF platforms, providing possibilities for devising anti-PD drugs.

Suggested Citation

  • Wei Jiang & Qing Li & Ruofei Zhang & Jianru Li & Qianyu Lin & Jingyun Li & Xinyao Zhou & Xiyun Yan & Kelong Fan, 2023. "Chiral metal-organic frameworks incorporating nanozymes as neuroinflammation inhibitors for managing Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43870-3
    DOI: 10.1038/s41467-023-43870-3
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    References listed on IDEAS

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