Recent advances in exosome-based nanodelivery systems for Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects dopaminergic neurons in the substantia nigra. Its multifactorial pathogenic mechanisms include oxidative stress, mitochondrial dysfunction, α-synuclein aggregation, neuroinflammation, and alterations in the gut microbiome, ultimately leading to neuronal deficits and debilitating motor and nonmotor symptoms. Although conventional therapies provide temporary relief, their efficacy tends to wane over time or produce adverse effects. Exosome-based therapeutic strategies are a promising alternative, and we highlight the unique advantages of exosomes, including their biocompatibility, low immunogenicity, and ability to cross the blood-brain barrier, thereby facilitating the targeted delivery of neuroprotective and anti-inflammatory medications to affected regions. We also discuss recent advances in exosome engineering to improve cargo loading, enhance cell specificity and improve efficacy. However, large-scale exosome production, targeted delivery and long-term safety remain major challenges. Early-phase clinical trials of exosome-based therapies in other neurodegenerative conditions have demonstrated acceptable tolerability, and ongoing preclinical studies in PD models suggest potential efficacy, laying the groundwork for future clinical translation.