Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery

Abstract

Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified liposomes, which led to the induction of cellular immunity in vivo. APCs express mannose receptors on their surface to recognize pathogen specifically and promote cross-presentation of antigen. In this study, mannose-residue was additionally introduced to carboxylated curdlan as a targeting moiety to APC for further improvement of polysaccharide-based antigen carriers. Mannose-modified curdlan derivatives were synthesized by the condensation between amino group-introduced mannose and carboxy group in pH-sensitive curdlan. Mannose residue-introduced carboxylated curdlan-modified liposomes showed higher pH-sensitivity than that of liposomes modified with conventional carboxylated curdlan. The introduction of mannose-residue to the liposomes induced aggregation in the presence of Concanavalin A, indicating that mannose residues were presented onto liposome surface. Mannose residue-introduced carboxylated curdlan-modified liposomes exhibited high and selective cellular association to APC. Furthermore, mannose residue-introduced carboxylated curdlan-modified liposomes promoted cross-presentation of antigen and induced strong antitumor effects on tumor-bearing mice. Therefore, these liposomes are promising as APC-specific antigen delivery systems for the induction of antigen-specific cellular immunity.

A splenic-targeted versatile antigen courier: iPSC wrapped in coalescent erythrocyte-liposome as tumor nanovaccine

“…At the same time, liposome as the drug carrier appears frequently in clinical treatment in recent years, which means that it has advantageous clinical transformed potentiality (31,32). The pair of mannose and mannose receptors can recognize and capture antigen molecules, promote antigen presentation, and regulate the maturation and differentiation of immune cells (33)(34)(35). Thus, we prepared mannose-modified liposomes to encourage the combination with APCs and stimulate maturation so as to activate the specific immunity of the body.…”

Application of Biomimetic Cell-Derived Nanoparticles with Mannose Modification as a Novel Vaccine Delivery Platform against Teleost Fish Viral Disease

“…Once antigens have more opportunities to be captured, processed, and presented by APCs, stronger immune response would be induced. , To enhance the internalization of NPs by APCs, different ligands were used to modify the surface of NPs. Owing to the high expression of mannose receptors on APCs, mannose is commonly used for the surface modification of nanocarriers. , Therefore, we modified the CS-G@M with mannose, which could specifically recognize the mannose receptor on teleost APCs. By flow cytometry, we found that, compared with CS-G@M without mannose modification, CS-G@M-M showed significantly enhanced cellular uptake by macrophages (Figure A,B).…”

“…Owing to the high expression of mannose receptors on APCs, mannose is commonly used for the surface modification of nanocarriers. 37,38 Therefore, we modified the CS-G@M with mannose, which could specifically recognize the mannose receptor on teleost APCs. By flow cytometry, we found that, compared with CS-G@M without mannose modification, CS-G@M-M showed significantly enhanced cellular uptake by macrophages (Figure 2A,B).…”

Preparation of glycopeptide-modified pH-sensitive liposomes for promoting antigen cross-presentation and induction of antigen-specific cellular immunity

“…To improve cross-presentation efficiency, mannose residues were introduced into carboxylated polysaccharide derivatives to promote their uptake selectivity to APCs and mannose receptor (MR)-mediated cross-presentation. 25 The mannose residue introduction increased the uptake selectivity considerably, but cross-presentation efficiency was not so improved, probably because the introduction of mannose residue into polysaccharide derivatives might have decreased the cytosolic delivery performance. 25…”

“…25 The mannose residue introduction increased the uptake selectivity considerably, but cross-presentation efficiency was not so improved, probably because the introduction of mannose residue into polysaccharide derivatives might have decreased the cytosolic delivery performance. 25…”