Tackling Allergic Airway Inflammation with Organic Sheet‐Like Nanoplatforms by Targeted Elimination of Epithelial Small Extracellular Vesicles

Allergic airway inflammatory disorders, such as allergic rhinitis (AR) and asthma, affect the health of more than one billion people worldwide, yet therapeutic outcomes remain unsatisfactory. 2D nanomaterials are extensively adopted in biomedical research, but their inorganic components often limit clinical applications. To address these challenges, functionalized "inorganic-free" nanosheets PNS_E are developed as a potential strategy for alleviating allergic inflammation via targeted elimination of epithelial small extracellular vesicles (sEVs). PNS_E are prepared using template-based synthesis technology and modified with epidermal growth factor receptor aptamers, which exhibit low cytotoxicity, mild protein adsorption, and potent epithelial sEVs binding efficacy. PNS_E suppresses sEVs-triggered stimulator of interferon genes activation, alleviating the dendritic cell maturation and eosinophil extracellular trap formation in vitro. In addition, PNS_E displays exceptional biocompatibility, preferential airway localization, and robust modulation for allergic airway inflammation in vivo. Transcriptome analysis and multi-channel flow cytometry of airway tissues further confirm the alleviation of dysregulated airway inflammation in house dust mite-stimulated animal models. These results highlight the pivotal feature of the organic sheet-like nanoplatforms for targeted clearance of epithelial sEVs, which can be exploited as a nanomedicine for the treatment of allergic airway inflammation and also other allergic disorders.