Nanotoxicity of iron oxide nanoparticle internalization in growing neurons

Magnetic nanoparticles (MNPs) have shown great promise for use as tools in a wide variety of biomedical applications, some of which require the delivery of large numbers of MNPs onto or into the cells of interest. Here we develop a quantifiable model cell system and show that intracellular delivery of even moderate levels of iron oxide (Fe₂O₃) nanoparticles may adversely affect cell function. More specifically, we show that exposure to increasing concentrations of anionic MNPs, from 0.15 to 15 mm of iron, results in a dose-dependent diminishing viability and capacity of PC12 cells to extend neurites in response to their putative biological cue, i.e. nerve growth factor. The cytotoxicity results of biomaterials in our model system imply that more study into the acute and long-term effects of cellular Fe₂O₃ internalization is both warranted and necessary.