Minimizing nonspecific phagocytic uptake of biocompatible gold nanoparticles with mixed charged zwitterionic surface modification

Abstract

Gold nanoparticles (AuNPs) with excellent resistance to phagocytic uptake by macrophages are achieved via a facile mixed charged zwitterionic self-assembled monolayers (SAMs) surface modification. A series of AuNPs with good dispersity against high salinity, strong resistance to plasma adsorption, persistent stability in cell culture medium and low cytotoxicity are prepared by surface modification with mixed charged SAMs in relatively wide range ratios of oppositely charged thiols. An in vitro study demonstrates that AuNPs modified by mixed charged SAMs effectively minimize the nonspecific cell uptake by either non-phagocytic HUVEC and HepG2 cells or phagocytic RAW 264.7 cells. When different factors that affect cell uptake including incubation time, nanoparticles concentration and incubation mode were evaluated, all results demonstrated that the resistance to phagocytosis by macrophage RAW 264.7 of the zwitterionic AuNPs is even much better than that of the traditional PEGylated AuNPs. A hemolysis assay with human erythrocytes demonstrates the good blood biocompatibility of the zwitterionic AuNPs. The excellent “stealth” properties of the mixed charged AuNPs promise their further biomedical applications both in vitro and in vivo.