• A nanozyme-integrated curcumin exosome biomimetic nanosystem (Cur-Exo@Pt-PB) was developed to efficiently traverse the blood–brain barrier via selective protein corona modulation. • Cur-Exo@Pt-PB synergistically alleviates oxidative stress and neuroinflammation, promoting microglial M1-to-M2 phenotype transition and protecting dopaminergic neurons in Parkinson’s disease models. • The nanosystem provides a multi-mechanistic and biomimetic therapeutic strategy, revealing previously underexplored nano-biological effects that advance the design of nanomedicine for neurodegenerative diseases. Oxidative stress and neuroinflammation are considered the major driving elements in the pathological process of Parkinson’s disease (PD). However, the presence of blood–brain barrier (BBB) in the brain restricts the efficiency of various anti-inflammatory drugs. Here, we present nanozyme-integrated curcumin exosome biomimetic nanosystem ( Cur-Exo@Pt-PB ) as an anti-neuroinflammatory agent with satisfactory BBB traversing ability for PD treatment. Cur-Exo@Pt-PB has multiple antioxidant enzyme activities and can efficiently eliminate reactive oxygen species. After intravenous injection, Cur-Exo@Pt-PB could adsorb more lipoproteins with less immunoglobulins and complement proteins in the blood, facilitating its BBB traversing and brain accumulation. Importantly, Cur-Exo@Pt-PB could effectively alleviate oxidative damage at the lesion site, improve the inflammatory microenvironment, and regulate the anti-inflammatory phenotypic transformation of microglia, thereby effectively improving the behavioral and pathological symptoms of PD. These results highlight the application of Cur-Exo@Pt-PB biomimetic nanosystem in the therapy of PD by boosting the BBB traversing and neuroinflammation relief.
Xu et al. (Sun,) studied this question.