Engineering fluorescent iNOS-Inhibitory covalent organic frameworks: Fewer doses than fluticasone propionate for...

Allergic rhinitis (AR) is a chronic inflammatory disease primarily mediated by T_H2-type immune responses, which is clinically managed with glucocorticoid therapy. However, this approach is limited by its variable efficacy and notable side effects. Herein, we developed two covalent organic framework (COF) nanoflakes-Aming-COF and Aming-BCOF-with inducible nitric oxide synthase (iNOS) inhibitory functions. We achieved targeted delivery and in vivo tracing by polymerizing the iNOS inhibitor aminoguanidine with a tetraphenylethylene fluorescent group through covalent bonds. In a mouse AR model induced by house dust mites, intranasal administration of Aming-COF demonstrated therapeutic efficacy: inhibiting excessive iNOS expression in the nasal mucosa to alleviate oxidative stress damage; repairing tight junction proteins such as ZO-1 and occludin to enhance epithelial barrier function; and regulating GATA-3/T-bet expression to rebalance T_H1/T_H2 immunity, thereby reducing T_H2-type cytokines such as IL-4 and IL-5 while increasing T_H1-type IFN-γ levels. Transcriptome analysis revealed its mechanism of action: inhibition of the IL5Rα-JAK-STAT signaling pathway. Aming-COF showed greater efficacy than fluticasone propionate with fewer doses (3 vs. 5) and no significant hepatotoxicity or nephrotoxicity, indicating good biosafety. This study provides a novel nanomaterial strategy for AR precision therapy and opens new directions for the application of COFs in immune regulation.