Plant-Derived Extracellular-Vesicle-Like Particles: Immune Regulation and Disease Therapy

Immune regulation is essential in both the pathogenesis and treatment of various diseases. Plant-derived extracellular-vesicle-like particles (PDEVLPs), especially herbal medicine, are emerging as promising cross-species nanotherapeutic carriers for immune regulation due to their intrinsic bioactive components. Compared with traditional small-molecule drugs, these natural nanocarriers offer superior pharmacokinetic properties in mammalian systems, including enhanced targeting capacity and penetration efficiency as well as prolonged circulation time. Due to the biogenic structures and low immunogenicity, most PDEVLPs exhibit generally favorable biocompatibility and substantial advantages in specific contexts. However, their immunological profile in humans, particularly the risk of immunogenicity from heterologous plant proteins, requires further investigation compared to established platforms such as liposomes. While diverse active ingredients endow PDEVLPs with effective regulation of various immune cells, they support body homeostasis and offer marked potential for treating multifactorial inflammatory and immune-related diseases. This review examines disease-specific immune microenvironments to provide a theoretical foundation for selecting PDEVLP-based therapies. It also evaluates engineering strategies to enhance the targeted delivery and therapeutic efficacy of these interkingdom mediators. By summarizing recent advancements, this review aims to guide the development of next-generation immune regulatory carriers tailored to specific microenvironments.