Plant-derived extracellular vesicles as emerging biotherapeutic agents and delivery vehicles for rheumatoid arthritis: evidence from preclinical models

Plant-derived extracellular vesicles (PDEVs) are emerging as promising natural nanotherapeutics for rheumatoid arthritis (RA). This review summarizes the therapeutic potential of PDEVs, highlighting their unique biological properties, multi-target mechanisms of action, and current application challenges. Accumulating evidence indicates that PDEVs can modulate immune responses, suppress inflammatory pathways, exert antioxidant effects, protect bone and cartilage, and influence the gut-joint axis. Meanwhile, engineering strategies, including drug loading, targeted modification and integration with smart materials, significantly enhance their therapeutic precision and stability. Despite their favorable biocompatibility and cross-barrier delivery potential, challenges such as insufficient standardization of isolation protocols, product heterogeneity, and limited mechanistic insight continue to hinder clinical translation. To date, the majority of studies have been conducted in cell culture or animal models, and clinical data remain unavailable. Future efforts should focus on standardization, in-depth mechanistic studies, and rigorous preclinical validation to accelerate clinical translation for RA and related inflammatory diseases.