Abstract
Abstract Biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) encapsulated with antigens can efficiently deliver the antigens to antigen-presenting cells such as dendritic cells (DCs). Active form of vitamin D, 1α,25-dihydroxyvitamin D3 (VD3), is known to have various immunosuppressive effects. Encapsulation of VD3 within NPs would enhance the delivery of VD3 to APCs, while preventing the potential systemic side effects of VD3. In this study, we examined the effects of PLGA NPs encapsulated with ovalbumin (OVA) and VD3. PLGA NPs containing OVA and VD3 (NP[OVA+VD3]) were prepared by W1/O/W2 double emulsion solvent evaporation method. Bone marrow-derived DCs treated with NP[OVA+VD3] were decreased in the expression of co-stimulatory molecules, and produced higher levels of immunosuppressive cytokines, while producing lower levels of pro-inflammatory cytokines, compared with DCs treated with NP[OVA]. Addition of NP[OVA+VD3] to allogeneic MLR reduced the proliferation of allogenic T cells. In addition, NP[OVA+VD3]-treated DCs efficiently generated CD4+CD25+Foxp3+Treg cells from CD4+CD25− T cells. Furthermore, mice injected i.v. with NP[OVA+VD3] were suppressed in inducing OVA-specific cytotoxic T cells. These results show that phagocytic delivery of antigen and VD3 to APCs using biodegradable NPs efficiently suppresses antigen-specific immune responses.
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