Plant-derived extracellular vesicles in cell-free therapeutics for neurological diseases

Plant-derived extracellular vesicles offer a promising frontier in nanomedicine for managing neurological diseases. This review systematically addresses their classification, botanical sources, isolation techniques, and biogenesis pathways. Comprehensive compositional analyses reveal a diverse cargo of proteins, lipids, nucleic acids, and metabolites that support their biological activity. Plant-derived extracellular vesicles possess intrinsic anti-inflammatory, antioxidant, antineoplastic, and regenerative properties, while also serving as efficient natural drug-delivery systems. We then summarize their therapeutic applications in nervous system tumors, traumatic neurological injuries, neurodegenerative diseases, and neuropsychiatric disorders. Although substantial challenges remain in standardizing isolation protocols and optimizing targeted delivery, plant-derived extracellular vesicles offer a sustainable, highly biocompatible, and scalable alternative to mammalian-derived extracellular vesicles. Future research should focus on harnessing their unique characteristics to improve cargo engineering and facilitate transport across physiological barriers, including the blood-brain barrier. Addressing these challenges and further optimizing the functionality of plant-derived extracellular vesicles could profoundly reshape the landscape of neurological therapeutics.