Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization

The efficient entry of nanotechnology-based pharmaceuticals into target cells is highly desired to reach high therapeutic efficiencywhile minimizing the side effects. Despite intensive research, the impact of the surface coating on the mechanism of nanoparticleuptake is not sufficiently understood yet. Herein, we present a mechanistic study of cellular internalization pathways of two magneticiron oxide nanoparticles (MNPs) differing in surface chemistry into A549 cells. The MNP uptake was investigated in the presenceof different inhibitors of endocytosis and monitored by spectroscopic and imaging techniques. The results revealed that theroute of MNP entry into cells strongly depends on the surface chemistry of the MNPs. While serum bovine albumin-coated MNPsentered the cells via clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis (CavME) or lipid rafts were preferentiallyinvolved in the internalization of polyethylene glycol-coated MNPs. Our data indicate that surface engineering can contribute toan enhanced delivery efficiency of nanoparticles.