Engineered extracellular vesicles-mediated curcumin delivery in brain microenvironment modulating lysosomes, mitochondria, and microglia reprogram for parkinson's disease therapy.

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons, aggregation of α-synuclein (α-Syn), lysosomal dysfunction, and mitochondrial impairment. Curcumin has demonstrated neuroprotective effects against PD pathology; however, its poor bioavailability, rapid systemic clearance, and limited blood-brain barrier permeability remain significant challenges to be overcome. An extracellular vesicle (EV)-based dopamine transporter (DAT)-targeted drug delivery system, derived from genetically engineered HEK293T cells, expressing DAT-targeting single-chain variable fragments (scFv) on the EV surface, is developed. Curcumin is encapsulated into the DAT-targeting EVs (αDAT EVs) for precise delivery into dopaminergic neurons. In the PD cell

SUBMITTER: Shie MY 

PROVIDER: S-EPMC12817626 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature