Decursin-loaded Poly-L-Lactic acid microspheres surface-functionalized with chemokine CCL17 alleviate allergic rhinitis by modulating regulatory T cells

Background: Decursin (Dec) has been identified as a potential component for treating allergic rhinitis (AR), but poor water solubility limits its application. This investigation intended to develop a novel drug delivery system to optimize the therapeutic effects of Dec. Methods: Dec@PLLA-CCL17 was prepared and its drug delivery performance was assessed. Tregs were treated with PLLA, PLLA-CCL17, Dec, Dec@PLLA, or Dec@PLLA-CCL17. Cell viability was detected by CCK-8 assay, and the association between microspheres and Tregs was visualized by laser confocal microscopy. IL-4, IL-10, and TGF- levels in Tregs were measured using ELISA. Ovalbumin-induced AR mice were administered with Dec@PLLA or Dec@PLLA-CCL17, and nasal scoring was conducted. Pathological changes of the nasal mucosa were evaluated through HE staining. Treg numbers was assessed using flow cytometry, and histamine, IL-4, IL-10, and TGF- levels were detected using ELISA. Apoptosis was assessed by TUNEL staining and Western blot. Results: Dec@PLLA-CCL17 showed favorable drug delivery properties. PLLA and PLLA-CCL17 had no effect on the viability of Tregs. Furthermore, Tregs exhibited a stronger association with Dec@PLLA-CCL17 than with Dec@PLLA. Dec, Dec@PLLA, and Dec@PLLA-CCL17 all remarkably increased cell viability and IL-10 and TGF- levels, while reducing IL-4 levels in Tregs, with Dec@PLLA-CCL17 having the strongest effect. In AR mice, both Dec@PLLA and Dec@PLLA-CCL17 notably reduced nasal symptom scores, alleviated nasal mucosal damage, increased Treg numbers, elevated IL-10 and TGF- levels, decreased histamine and IL-4 levels, and reduced apoptosis, with Dec@PLLA-CCL17 showing superior effects. Conclusion: Dec@PLLA-CCL17 alleviates allergic rhinitis by enhancing the proliferation and immunosuppressive function of Tregs.