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

Haibo Feng,Xiaonong Yang,Yangyang Feng,Daiyan Wu,Jie Yang,Yunjie Liu,Qianqian Liu,Linzi Zhang

doi:10.3390/polym13132208

Haibo Feng, Xiaonong Yang + Show 6 more

Open Access

https://doi.org/10.3390/polym13132208

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Journal: Polymers	Publication Date: Jul 3, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Southwest Minzu University, Southwest University

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.

Highlights

Chitosan (CS), known as deacetylated chitin, is prepared by deacetylation of chitin
The present results indicate that MANCS-poly(lactic-co-glycolic acid) (PLGA)-MPs significantly promoted the expression of CD80+, CD86+, and MHC II in mice spleen dendritic cells (DCs) cells, which confirmed that MAN-CS-PLGA-MPs more strongly activated the maturation of DCs compared with the other MPs
We showed that MAN-CS-OVA-PLGA-MPs acted as an MR-targeting antigen delivery system that significantly enhanced the cellular and humoral immune response via facilitating the maturation of DCsRAW264.7

Summary

Introduction

Chitosan (CS), known as deacetylated chitin, is prepared by deacetylation of chitin. Pure CS is a translucent white powder that is very difficult to dissolve in water and acid and can be completely absorbed by the body [1]. It has good biocompatibility, anti-inflammatory, antibacterial, antioxidation, blood lipid and glucose reduction, immune regulation, and other biological activities [2,3,4,5]. As a natural nontoxic adjuvant, CS protects the activity of the antigen and enhances the immune response of immune cells to the antigen. CS has a better vaccine protection effect. Its stable electrostatic binding ability prevents the vaccine from being enzymolyzed before reaching the target cells and maintains the integrity and stability of the original structure of the antibody, and this combination will produce an improved immune effect compared with the direct application of the vaccine [7]

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Discussion

Conclusion