Plant-derived extracellular vesicles in allergic diseases: From immunomodulatory nanotherapeutics to environmental allergen carriers

Plant-derived extracellular vesicles (PDEVs) are increasingly investigated as naturally bioactive nanovesicles and as carriers for exogenous therapeutics. Their lipids, proteins, small RNAs, and secondary metabolites can influence immune-cell function, epithelial integrity, oxidative stress, and host-microbiota interactions. However, the relevance of this evidence to allergic disease is uneven. Direct allergy-specific evidence currently includes a limited number of preclinical studies, most notably Aster yomena callus-derived EVs in allergic asthma, whereas many mechanistic claims are extrapolated from colitis, infection, cancer, vascular, or wound-healing models. In parallel, environmental vesicles can promote disease rather than resolve it. Pollen-derived vesicles (pollensomes) and allergen-bearing EVs in indoor dust can protect and co-deliver allergenic proteins, lipid mediators, oxidases, and adjuvant-like signals, thereby facilitating epithelial exposure and type 2 immune activation. This review critically integrates these opposing vesicle contexts. We summarize PDEV biogenesis, isolation, composition, characterization, engineering, loading, and biodistribution; distinguish direct allergic-disease evidence from indirect mechanistic support; and place vesicle actions within the epithelial alarmin-ILC2-Th2-IgE axis and regulatory T-cell, regulatory B-cell, and IgG4-associated tolerance. We further define critical quality attributes, allergenicity testing, release criteria, regulatory considerations, and patient-stratification requirements. PDEVs may offer useful opportunities for allergy nanomedicine, but their translation will require source-specific characterization, rigorous potency and safety assays, and avoidance of unqualified extrapolation from non-allergic models.