Extracellular Vesicle-Delivered VEGF and NGF Improve Motor Function, Dopaminergic Neuron Survival in Parkinson's Rat Models

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons, leading to severe motor dysfunction. Current therapies primarily offer symptomatic relief, failing to halt or reverse neuronal damage. Vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) are potent neuroprotective agents, but their large molecular size prevents effective crossing of the blood-brain barrier (BBB). Extracellular vesicles (EVs) offer a promising solution as natural nanocarriers, providing superior targeting, low immunogenicity, and the ability to deliver therapeutic cargo across the BBB, addressing a critical gap in neurorestorative strategies for PD.

Extracellular vesicles (EVs) were isolated and loaded with VEGF and NGF using a saponin-assisted method, creating VEGF@EVs, NGF@EVs, and VEGF/NGF@EVs. The study first assessed viability of 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y cells using CCK-8 assay, evaluating protection. Autophagy levels were measured by Western blotting, with chloroquine exploring its role. Unilateral PD rat models were established via stereotactic 6-OHDA injection into male Sprague-Dawley rats. Behavioral changes were monitored, and neuronal recovery, neurotransmitter levels, and autophagy were assessed post-treatment via immunohistochemistry, ELISA, and Western blotting.