Cellular distribution of polymer particles bearing various densities of carbohydrate ligands

The density effect of carbohydrate-ligands on nanometer-order particles (nanoparticles) upon cellular binding and internalization was investigated. Poly(vinylbenzyl-beta-D-lactonamide) (PVLA), a beta-galactose-carrying styrene homopolymer, was employed as a model ligand for the asialoglycoprotein receptors on hepatocytes. In order to control the surface ligand densities on the particles, PVLA was mixed with poly(vinylbenzyl-D-gluconamide) (PVGA), a PVLA analog without beta-galactose, and their mixtures were used as surface coatings. The particles with low ligand densities associated more with hepatocytes than high ligand density particles. The surface density of the ligand considerably influenced the cellular distribution. Most of the particles bearing high densities of ligands were found inside the cells, whereas particles with low ligand densities were found on the plasma membrane surface of the hepatocytes. These results were indicative of high densities of ligands on the surface requiring hepatocytes to internalize the particles promptly by receptor-mediated endocytosis, while low densities of ligands on the surface was not sufficient to internalize, but allowed particles to bind on the cell surface. These findings enabled us to regulate cellular distributions of particles by controlling ligand density on the surface.