Investigation of plasma protein adsorption on functionalized nanoparticlesfor application in apheresis

Particles with specific ligands for the adsorption of plasma proteins can b e used in therapeutic or preparative apheresis. The development of these pa rticles may benefit from an improved knowledge of the relationship between protein adsorption and the structure of ligands. Nanoparticles were functio nalized with aliphatic diamines of increasing chain length; with the amino acids lysine, tryptophan, histidine, and their corresponding amines; and wi th tryptophan and histidine spaced with diamines of different length. Suita ble protocols were developed for the washing of particles and the subsequen t desorption of proteins adsorbed from human plasma. The adsorption pattern , as well as the quantification of the overall adsorption of proteins on th ese modified particles, was investigated with gel electrophoresis. This was followed by immunoblotting which yielded specific assessments of bound hum an serum albumin and fibrinogen. The comparison of protein adsorption with surface charge density and measured hydrophobicities yielded no simple corr elations although in general more hydrophobic ligands bound higher quantiti es of protein. The detection of human serum albumin yielded similar results because it was observed for overall protein adsorption while the adsorptio n of fibrinogen expressed a different pattern. In this case, particular nan oparticles functionalized with aliphatic diamines bound significantly highe r amounts of fibrinogen than all other ligands.