Mannose-Modified Chitosan Poly(lactic-co-glycolic acid) Microspheres Act as a Mannose Receptor-Mediated Delivery System Enhancing the Immune Response

Abstract

The mannose receptor (MAN-R)-targeted delivery system is commonly used to deliver antigens to macrophages or immature dendritic cells (DCs) to promote the efficiency of antigen presentation. To maximize the enhancement effects of chitosan (CS) and induce an efficient humoral and cellular immune response against an antigen, we encapsulated ovalbumin (OVA) in poly(lactic-co-glycolic acid) (PLGA) microspheres (MPs) and conjugated it with MAN-modified CS to obtain MAN-R-targeting nano-MPs (MAN-CS-OVA-PLGA-MPs). The physicochemical properties, drug loading rate, and immunomodulation activity of MAN-CS-OVA-PLGA-MPs were evaluated. In vitro, MAN-CS-OVA-PLGA-MPs (80 μg mL−1) could enhance the proliferation of DCs and increase their phagocytic efficiency. In vivo, MAN-CS-OVA-PLGA-MPs significantly increased the ratio of CD3+CD4+/CD3+CD8+ T cells, increased CD80+, CD86+, and MHC II expression in DCs, and improved OVA-specific IgG, IgG1, IgG2a, and IgG2b antibodies. Moreover, MAN-CS-OVA-PLGA-MPs promoted cytokine (IFN-γ, IL-4, and IL-6) production in mice. Taken together, our results show that MAN-CS-OVA-PLGA-MPs may act by activating the T cells to initiate an immune response by promoting the maturation of dendritic cells and improving their antigen presentation efficiency. The current study provides a basis for the use of MAN-CS-OVA-PLGA-MPs as an antigen and adjuvant delivery system targeting the MAN-R on the surface of macrophages and dendritic cells.