Engineered Exosomes: Innovative Strategies for Precision Drug Delivery in Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disorder marked by dopaminergic neuron loss in the substantia nigra, pathological α-synuclein aggregation, and persistent neuroinflammation. Current therapies mainly offer symptomatic relief but do not halt or reverse disease progression, largely because of the restrictive blood-brain barrier. Exosomes, naturally occurring nanoscale vesicles, possess key attributes such as biocompatibility, low immunogenicity, and the capacity to cross the blood-brain barrier. In Parkinson's disease, exosomes have a dual role: they propagate α-syn pathology and amplify inflammatory signaling, accelerating disease progression; conversely, they can be engineered as carriers of neurotrophic factors, microRNAs, or small-molecule drugs, conferring neuroprotective and anti-inflammatory benefits. This review examines current strategies for exosome engineering, with emphasis on surface modification and optimized cargo loading. However, clinical translation remains hindered by suboptimal delivery efficiency, limited brain accumulation, potential immunogenicity, exosome heterogeneity, and regulatory barriers. Future research should prioritize high-affinity targeting ligands, multimodal delivery platforms, deeper insights into blood-brain barrier translocation, and integration with regenerative medicine approaches. These advancements are essential for standardized large-scale production and personalized therapies, ultimately advancing precision medicine in Parkinson's disease.