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

• Published in: Nature communications Vol. 14; no. 1; pp. 8137 - 18
• Main Authors: Jiang, Wei, Li, Qing, Zhang, Ruofei, Li, Jianru, Lin, Qianyu, Li, Jingyun, Zhou, Xinyao, Yan, Xiyun, Fan, Kelong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.12.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/2; 13/31; 13/51; 14/19; 14/63; 140/146; 147/143; 38/91; 639/301/54/990; 639/638/92/152; 639/638/92/603; 692/699/375/1718; 82/51; Animal models; Animals; Antioxidants; Apoptosis; Bioinformatics; Blood-brain barrier; Caveolae; Clathrin; Drugs; Embedding; Endocytosis; Ferroptosis; Humanities and Social Sciences; Inflammation; Male; Metal-organic frameworks; Metal-Organic Frameworks - pharmacology; Mice; Movement disorders; multidisciplinary; Nanotechnology; Neurodegenerative diseases; Neuroinflammatory Diseases; Parkinson Disease - drug therapy; Parkinson's disease; Science; Science (multidisciplinary); Tissue Distribution; Zeolites
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43870-3

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. The treatment of Parkinson’s disease (PD) is hampered by the lack of effective blood–brain barrier (BBB) traversing drugs. Here, the authors report nanozyme-integrated metal-organic frameworks with antioxidant activity and chiral-dependent BBB transendocytosis as anti-neuroinflammatory agents for PD treatment.