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

Wei Jiang, Qing Li (), Ruofei Zhang, Jianru Li, Qianyu Lin, Jingyun Li, Xinyao Zhou, Xiyun Yan () and Kelong Fan ()
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Wei Jiang: the Second Affiliated Hospital of 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
Xinyao Zhou: University of Pennsylvania
Xiyun Yan: Zhengzhou University
Kelong Fan: Zhengzhou University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43870-3

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