Glycopolymers With On/Off Anchors: Confinement Effect on Regulating Dendritic Cells

Insufficient activation or over-activation of T cells due to the dendritic cells (DCs) state can cause negative effects on immunotherapy, making it crucial for DCs to maintain different states in different treatments. Polysaccharides are one of the most studied substances to promote DCs maturation. However, in many methods, optimizing the spatial dimension of the interaction between polysaccharides and cells is often overlooked. Therefore, in this study, a new strategy from the perspective of spatial dimension is proposed to regulate the efficacy of polysaccharides in promoting DCs maturation. An anchoring molecule (DMA) is introduced to existing glycopolymers for the confinement effect, and the effect can be turned off by oxidation of DMA. Among the prepared on-confined (PMD2), off-confined (PMD2-O), and norm (PM2) glycopolymers, PMD2 and PMD2-O show the best and worst results, respectively, in terms of the amount of binding to DCs and the effect on promoting DCs maturation. This sufficiently shows that the turn-on and off of confinement effect can regulate the maturation of DCs by polysaccharides. Based on the all-atom molecular dynamics (MD) simulation, the mechanism of difference in the confinement effect is explained. This simple method can also be used to regulate other molecule-cell interactions to guide cell behavior.