Resveratrol-integrated Se-chitosan nanogel for protein corona-mediated blood-brain barrier traversing and anti-inflammatory treatment for Parkinson's disease
Yuan Cao, Linwei Zhao, Qing Li, Bo Song, Yuming Xu, Lin Jiang, Shaohua Li
Abstract
Anti-inflammatory strategies have become a promising dawn of Parkinson's disease (PD) therapy. However, the efficiency and clinical transformation prospects of anti-inflammatory strategies are worth considering concerning the effects of traversing the blood-brain barrier (BBB) and subsequent inflammation mitigation. Here, we report resveratrol (Res) and Se-chitosan (CS) integrated nanogel (Res@SeN) as an anti-neuroinflammatory agent for the treatment of PD. Network pharmacological analyses explained that Res acts on PD through neuroinflammation-related factors and pathways. Additionally, Res assists nanogels in adsorbing more lipoproteins in the blood, altering the protein corona composition, thereby facilitating Res@SeN to traverse the BBB and accumulate more efficiently in the brain. Res@SeN can alleviate oxidative stress and the pathological symptoms of PD, regulating the anti-inflammatory phenotypic transformation of microglia. Transcriptomic studies have found that the remission of PD inflammation by Res@SeN is associated to the NF-kappa B and TGF-β signaling pathways. In summary, our findings highlight the clinical transformation prospects of Res and Se-integrated nanogel system in the symptom relief of PD via enhancing the BBB traversing and neuroinflammation relief.