Extracellular Vesicle-Based Immunomodulation in Autoimmune Encephalitis: Novel Therapeutic Approaches Using Engineered Exosomes for CNS Drug Delivery

Abstract

Autoimmune encephalitis represents a severe neurological condition characterized by immune-mediated inflammation of the central nervous system, resulting in significant morbidity and neurological sequelae. Current therapeutic interventions, including immunosuppressive agents and plasmapheresis, often demonstrate limited efficacy and substantial systemic adverse effects. Extracellular vesicles, particularly exosomes, have emerged as promising nanoscale therapeutic vehicles capable of crossing the blood-brain barrier and delivering immunomodulatory cargo to affected neural tissues. This comprehensive review explores the fundamental biology of extracellular vesicles, their intrinsic immunomodulatory properties, and recent advances in engineering exosome-based therapeutics for autoimmune encephalitis management. We examine the molecular mechanisms underlying exosome-mediated immunosuppression, discuss innovative bioengineering strategies for targeted CNS delivery, and evaluate preclinical evidence supporting their therapeutic potential. Furthermore, we address critical challenges including standardization of production methods, biodistribution optimization, and regulatory considerations for clinical translation. The integration of extracellular vesicle technology with precision medicine approaches represents a paradigm shift in treating autoimmune neurological disorders, offering unprecedented opportunities for personalized, minimally invasive interventions with enhanced therapeutic indices compared to conventional treatments.