De Novo developing nanoplatform encapsuling α-arbutin and α-syn inhibitor for precise treatment of Parkinson's disease.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by progressive degeneration of dopaminergic neurons in the midbrain. Currently, PD remains incurable, though administration of levodopa or deep brain stimulation could partially ameliorate symptoms of PD. Mechanistically, PD is underlined by mitochondrial dysfunction, oxidative stress, α-synuclein (α-Syn) aggregation and neuroinflammation. Hence, intervention targeting those pathogenetic factors hold great potential for effective treatment of PD. In present study, we developed one nanoplatform encapsuling natural antioxidant (α-arbutin) and α-synuclein inhibitor (Anle138b) for precise treatment of PD by blood brain barrier (BBB) penetrating peptide facilitated intra brain delivery. The endowed property of as developed nanoplatform, HMPDA@AA/RVG, was were characterized. Both in vitro and in vivo experiments confirmed that HMPDA@AA/RVG exerted neuroprotective effects by ameliorating oxidative stress, mitochondrial dysfunction and α-Syn aggregation. HMPDA@AA/RVG was specifically distributed in the brain, successfully rescued dopaminergic neuron loss and the behavioral deficits of PD mice. In summary, by targeting multiple pathological features of PD, we developed one multiple functional nanoplatform for that effectively mitigated PD phenotypes. Our study paves the way for precise intervention of neurodegenerative diseases by leveraging the nanomaterials facilitated delivery of natural medicine and chemical compounds.