A Dual Synergetic Nanoreactor for Managing Parkinson's Disease by Regulating Inflammation and Mitigating Oxidative Damage

Abstract Glial cell‐dominated inflammatory microenvironment and neuronal damage due to oxidative stress are major impediments to the treatment of central nervous degenerative diseases. Herein, a neuroinflammatory regulatory nanoreactor is developed by encapsulating dihydroquercetin (Que) and Pt nanozymes (Ptzymes) in mannitol modified poly(lactic‐ co ‐glycolic acid) nanoparticles. The nanoreactor shows enhanced antioxidative activities compared with either Que or Ptzymes alone due to synergetic effects of the incorporated active agents. In cellular and animal models of Parkinson's disease (PD), the nanoreactor traverses the blood–brain barrier and accumulates in neurons and microglia, thereby mitigating oxidative damage of neurons, and promoting the polarization of microglia into the anti‐inflammatory M2‐phenotype to control PD progression. This work demonstrates the gains of combining anti‐inflammation small molecule compound and antioxidant nanozyme in a synergetic nanoreactor to effectively prevent neuronal damage and suppress the inflammatory microenvironment, which holds great potential for managing the advances of PD.