Polymeric Nanoparticles Containing Both Antigen and Vitamin D₃ Induce Antigen-Specific Immune Suppression

The active form of vitamin D₃, 1,25-dihydroxyvitamin D₃ (aVD₃), is known to exert beneficial effects in the treatment of autoimmune diseases because of its immunosuppressive effects. However, clinical application of aVD₃ remains limited because of the potential side effects, particularly hypercalcemia. Encapsulation of aVD₃ within biodegradable nanoparticles (NPs) would enhance the delivery of aVD₃ to antigen presenting cells, while preventing the potential systemic side effects of aVD₃. In the present study, polymeric NPs containing ovalbumin (OVA) and aVD₃ (NP[OVA+aVD₃]) were prepared via the water-in-oil-in-water double emulsion solvent evaporation method, after which their immunomodulatory effects were examined. Bone marrow-derived immature dendritic cells (DCs) treated with NP(OVA+aVD₃) did not mature into immunogenic DCs but were converted into tolerogenic DCs, which express low levels of co-stimulatory molecules and MHC class II molecules, produce lower levels of pro-inflammatory cytokines while increasing the production of IL-10 and TGF-β, and induce the generation of Tregs. Intravenous injection with NP(OVA+aVD₃) markedly suppressed the generation of OVA-specific CTLs in mice. Furthermore, OVA-specific immune tolerance was induced in mice orally administered with NP(OVA+aVD₃). These results show that biodegradable NPs encapsulating both antigen and aVD₃ can effectively induce antigen-specific immune suppression.