Extracellular vesicles in atopic dermatitis: unraveling pathogenic mediators and engineering therapeutic vectors

Atopic dermatitis (AD) is a complex chronic inflammatory skin disease whose pathogenesis involves a vicious cycle of epidermal barrier defects, immune dysregulation, and microbial imbalance. Despite advances in targeted biologics and small-molecule drugs, there remains an unmet clinical need for safe, effective treatments that can simultaneously intervene in multiple pathological processes. Extracellular vesicles (EVs), as key mediators of intercellular communication, play an increasingly prominent dual role in the pathophysiology and treatment of AD. This review systematically elaborates on this dialectical unity of EVs in AD. In terms of pathological mechanisms, EVs derived from pathogens such as Staphylococcus aureus and Malassezia spp., as well as from host mast cells, act as active "nanoscale pathological messengers" that deeply participate in disease initiation and progression by delivering virulence factors, disrupting the skin barrier, driving Th2/Th17 immune polarization, and sustaining chronic inflammation. Regarding therapeutic applications, therapeutic EVs derived from mesenchymal stem cells (e.g., adipose-, umbilical cord-derived), plants, probiotics, and marine organisms serve as efficient "cell-free therapeutic platforms, " demonstrating great potential for intervening in AD through multipathway immunomodulation, active restoration of barrier function, and systemic regulation of the gut-skin axis. Moreover, strategies such as preconditioning parental cells (e.g., hypoxia, cytokine stimulation), genetic engineering, or constructing hybrid EVs can further enhance the therapeutic efficacy of EVs; combining them with advanced delivery systems (e.g., hydrogels, microneedles) can effectively overcome transdermal delivery bottlenecks. Although promising, the field still faces challenges including uneven source selection, lack of standardization in preparation and characterization, insufficient mechanistic elucidation, limitations of preclinical models, and inadequate pharmacokinetic and long-term safety data. Future research should focus on establishing standardized protocols, deepening mechanistic understanding, developing more accurate disease models, and exploring translational avenues to assess the potential for next-generation precision diagnostic and therapeutic strategies for AD based on EVs.