Lentinan‐Enhanced Mn ₃ O ₄ Nanoparticles for Neuroinflammation Relief and Parkinson's Disease Treatment

ABSTRACT Neuroinflammation plays an irreplaceable part in the pathogenesis and progression of Parkinson's disease (PD). While anti‐inflammatory nanomedicine offers new hope for PD treatment, the nano‐biological effects that govern their therapeutic outcomes remain largely unexplored. Herein, after investigating the mechanism of action of lentinan (LNT) on PD by network pharmacology, we report LNT and Mn ₃ O ₄ integrated nanosystems (Mn ₃ O ₄ @LNT) as anti‐neuroinflammatory agents for PD treatment. Proteomics analyses found that there are significant differences in protein corona composition between Mn ₃ O ₄ and Mn ₃ O ₄ @LNT, and the protein coronas in Mn ₃ O ₄ @LNT are beneficial for BBB traversing and brian accumulation. In vivo and in vitro studies have shown that Mn ₃ O ₄ @LNT effectively alleviates the behavioral and pathological symptoms of PD by eliminating reactive oxygen species and reducing neuroinflammation. Transcriptomics further revealed the vital part of the phenotypic transformation of microglia and inflammatory response in the action of Mn ₃ O ₄ @LNT on the PD model. In summary, our study highlights the clinical application prospects of Mn ₃ O ₄ @LNT by benefiting the BBB traversing and promoting neuroinflammation mitigation in PD models.