Immune Effect Regulated by the Chain Length: Interaction between Immune Cell Surface Receptors and Synthetic Glycopolymers

Abstract

Glycopolymer-based drugs for immunotherapy have attracted increasing attention because the affinity between glycans and proteins plays an important role in immune responses. Previous studies indicate that the polymer chain length influences the affinity. In the studies on enhancing the immune response by glycans, it is found that both oligosaccharides and long-chain glycopolymers work well. However, there is a lack of systematic studies on the immune enhancement effect and the binding ability of oligomers and polymers to immune-related proteins. In this paper, to study the influence of the chain length, glycopolymers based on N-acetylglucosamine with different chain lengths were synthesized, and their interaction with immune-related proteins and their effect on dendritic cell maturation were evaluated. It was proved that compared with l-glycopolymers (degree of polymerization (DP) > 20), s-glycopolymers (DP < 20) showed better binding ability to the dendritic cell-specific ICAM-3-grabbing nonintegrin protein and the toll-like receptor 4 and myeloid differentiation factor 2 complex protein by quartz crystal microbalance and molecular docking simulation. When the total sugar unit amounts are equal, s-glycopolymers are proved to be superior in promoting dendritic cell maturation by detecting the expression level of CD80 and CD86 on the surface of dendritic cells. Through the combination of experimental characterization and theoretical simulation, a deep look into the interaction between immune-related proteins and glycopolymers with different chain lengths is helpful to improve the understanding of the immune-related interactions and provides a good theoretical basis for the design of new glycopolymer-based immune drugs.

Glycopolymer Engineering of the Cell Surface Changes the Single Cell Migratory Direction and Inhibits the Collective Migration of Cancer Cells

“…Matured dendritic cells (DCs) can activate initial T cells and eventually lead to the killing of cancer cells. Many glyco-receptors are expressed on immature DCs, and previous studies have shown that it is possible to use glycopolymers to promote the maturation of DCs . Glycopolymer-modified cancer cells, in addition to changing the migratory behavior, are expected to interact with dendritic cells (DCs) and promote the maturation of DCs.…”

“…Many glyco-receptors are expressed on immature DCs, 19 and previous studies have shown that it is possible to use glycopolymers to promote the maturation of DCs. 32 Glycopolymer-modified cancer cells, in addition to changing the migratory behavior, are expected to interact with dendritic cells (DCs) and promote the maturation of DCs. Here we investigate the stimulating effect of glycopolymer-modified B16 cells on the maturation of primary DCs.…”

Tailor-made glycopolymersviareversible deactivation radical polymerization: design, properties and applications

“…Their findings indicate that longer macromolecular chains do not always lead to better binding for designing glycopolymers for immune-related proteins. 69…”

In situ preparation of glyco-micromotors and their bacteria loading/guiding ability

“…This journal is © The Royal Society of Chemistry 2022 sugar-based adjuvants for immunotherapy, 34,35 and the intelligent drug delivery by pH-responsive polymers and photolysis. 36 Of course, the cytotoxicity of the micromotors also needs to be considered in applications.…”

“…More importantly, the directional motion of the complexes can be made by applying a non-uniform UV light field at a high packing fraction. With their motion capability, polymer-by-design ability, and pH-changing property, the glyco-micromotors demonstrated extensive application potential, for example, in the isolation of biological targets from mixtures, 29,30 the neutralization of toxins, 31–33 the transportation of sugar-based adjuvants for immunotherapy, 34,35 and the intelligent drug delivery by pH-responsive polymers and photolysis. 36 Of course, the cytotoxicity of the micromotors also needs to be considered in applications.…”