Metal-Organic Framework Based Nanozyme for NLRP3 Inflammasome-Mediated Neuroinflammatory Regulation in Parkinson's Disease.

Neuroinflammation is associated with a series of pathological symptoms in Parkinson's disease (PD), including α-synuclein accumulation and dopaminergic neuronal death. The NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation at the lesion site and is a promising target for PD treatment. In this study, a nanoscale metal-organic framework (Zr-FeP MOF) based nanozyme is fabricated using Fe-5,10,15,20-tetra (4-carboxyphenyl) porphyrin (Fe-TCPP) and Zr 6 cluster as ligands. Zr-FeP MOF is then encapsulated using mannitol-liposome to form Zr-FeP MOF@Man Liposome nanozyme (MOF@Man Liposome). The in vitro studies show this nanozyme is effective in relieving the formation of NLRP3 inflammasome and mitochondrial dysfunction. In a mouse model of PD, the nanozyme demonstrates a significant blood-brain barrier-crossing capability attributed to the mannitol-mediated brain targeting. Additionally, transcriptomic and biochemical studies show that the nanozyme effectively inhibits the formation and assembly of inflammasome components, mitigating the activation of glial cells and neuroinflammatory response, and ultimately regulating the pathological symptoms of PD effectively. This article is protected by copyright. All rights reserved.