Preclinical study showing lentinan-coated Mn3O4 nanoparticles (Mn3O4@LNT) alter protein corona to enhance BBB penetration, scavenge ROS, shift microglial phenotype, and reduce behavioral and pathological features in PD models.

Provides mechanistic and translationally relevant evidence that a nanoparticle combining enhanced brain delivery with ROS elimination and anti-neuroinflammatory effects can ameliorate PD phenotypes, highlighting a promising therapeutic strategy while raising important safety and manganese-toxicity…

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 Mn3O4 integrated nanosystems (Mn3O4@LNT) as anti-neuroinflammatory agents for PD treatment. Proteomics analyses found that there are significant differences in protein corona composition between Mn3O4 and Mn3O4@LNT, and the protein coronas in Mn3O4@LNT are beneficial for BBB traversing and brian accumulation. In vivo and in vitro studies have shown that Mn3O4@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 Mn3O4@LNT on the PD model. In summary, our study highlights the clinical application prospects of Mn3O4@LNT by benefiting the BBB traversing and promoting neuroinflammation mitigation in PD models.