Differences in surface chemistry of iron oxide nanoparticles result in different routes of internalization
April 2021
The efficient entry of nanotechnology-based pharmaceuticals into target cells is highly desired to reach high therapeutic efficiency while minimizing the side effects. Despite intensive research, the impact of the surface coating on the mechanism of nanoparticle uptake is not sufficiently understood yet. Herein, we present a mechanistic study of cellular internalization pathways of two magnetic iron oxide nanoparticles (MNPs) differing in surface chemistry into A549 cells. The MNP uptake was investigated in the presence of different inhibitors of endocytosis and monitored by spectroscopic and imaging techniques. The results revealed that the route of MNP entry into cells strongly depends on the surface chemistry of the MNPs. While serum bovine albumin-coated MNPs entered the cells via clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis (CavME) or lipid rafts were preferentially involved in the internalization of polyethylene glycol-coated MNPs. Our data indicate that surface engineering can contribute to an enhanced delivery efficiency of nanoparticles.
Efficient cellular internalization of nanoparticles is one of the critical steps during the development of new nanotechnology-based pharmaceuticals.
MNPs coated with bovine serum albumin (BSA-SO-MNPs) and polyethylene glycol (PEG-SO-MNPs), were found to enter the cells by different routes of endocytosis. BSA-SO-MNPs were internalized via CME while PEG-SO-MNPs were taken up via CavME or lipid rafts. These findings confirm the major role of nanoparticle coatings on cellular entry mechanisms. Our data suggest that the effects of endocytic inhibitors on the internalization pathways are rather complex. MNPs may be internalized by several endocytic pathways simultaneously, although with varying efficiency, and inhibition of one endocytic pathway can subsequently stimulate other routes of their internalization. Understanding the mechanisms of cellular uptake is of particular importance for the design of new nanotechnology-based pharmaceuticals and their targeting to specific intracellular locations…