Metal–Organic Framework Based Nanozyme System for NLRP3 Inflammasome‐Mediated Neuroinflammatory Regulation in Parkinson's Disease

Abstract Neuroinflammation is associated with a series of pathological symptoms in Parkinson's disease (PD), including α‐synuclein aggregation 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. The Zr‐FeP MOF is subsequently encapsulated with mannitol (Man)‐liposome, resulting in the formation of Zr‐FeP MOF@Man liposome (MOF@Man Liposome) nanozyme system. The in vitro studies show that this nanozyme system is effective in relieving the formation of NLRP3 inflammasome and mitochondrial dysfunction. In mouse models of PD, the nanozyme system demonstrates a significant blood–brain barrier‐crossing capability attributed to the Man‐mediated brain targeting. Additionally, transcriptomic and biochemical studies show that the nanozyme system 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.