Objective  To construct a nanoparticle-based carrier capable of restoring airway immunoregulatory function under allergic conditions, and evaluate its immunomodulatory effects and potential therapeutic value against allergic airway inflammation.

Methods  Vasoactive intestinal peptide (VIP)-loaded nanoparticles (VIP NPs) were prepared using a double-emulsion method and further modified with an MHC-Ⅱ/OVA epitope peptide fusion protein to generate MOV nanoparticles (MOV NPs). The physicochemical properties and in vitro release profile of MOV NPs were characterized. An ovalbumin (OVA)-induced murine model of allergic airway disease was established and treated with different doses of MOV NPs. Serum allergen-specific antibodies, inflammatory mediators and Th2 cytokines in bronchoalveolar lavage fluid (BALF) were measured. Flow cytometry and functional assays were performed to analyze the abundance and suppressive activity of regulatory T cells (Tregs) in airway tissues. The expression levels of Treg-associated cytokines, transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) were further determined.

Results  MOV NPs exhibited a uniform spherical morphology, negative surface charge, stable sustained-release properties, and a VIP encapsulation efficiency of (63.12 ± 2.15)%. MOV NPs treatment significantly reduced serum sIgG1 and sIgE levels, as well as BALF inflammatory mediators and Th2 type cytokines, in a dose-dependent manner. Compared with the model group, MOV NPs markedly increased the number and immunosuppressive function of airway Tregs, and up-regulated the expression levels of TGF-β and IL-10.

Conclusion  MOV NPs integrate dual functions of antigen presentation and VIP-mediated immunoregulation, which can effectively inhibit airway allergic inflammation and restore local immune homeostasis.