Cellular Glycocalyx Affects Nanoparticle Access to Cell Membranes and Uptake

Abstract Understanding nanoparticle interactions with cells is fundamental to designing them for medical applications. Nanoparticles must interface with the cell surface to be bound and taken up. The glycocalyx is a carbohydrate layer coating the cell surface, rendering it negatively charged. Many researchers have noted that the glycocalyx affects nanoparticle uptake, but the mechanism remains unknown, Here, we investigate the interaction between the glycocalyx and nanoparticles at the cell surface in different cell types. The glycocalyx reduced the interactions between the nanoparticles and cells, thereby reducing cellular access, binding, and uptake. The magnitude of the effect is dependent on the nanoparticle charge. Fine‐tuning the charge of nanoparticles can enhance the specificity of nanoparticle targeting. Understanding the role of the glycocalyx in nano‐bio interactions will allow researchers to control the interactions of nanoparticles with the cell surface.