Neurotoxicity assessment of oleic acid-coated iron oxide nanoparticles in SH-SY5Y cells

Iron oxide nanoparticles (ION) awaken a particular interest for biomedical applications due to their unique physicochemical properties, especially superparamagnetism, and ability to cross the blood-brain barrier. ION surface can be coated to improve their properties and facilitate functionalization. Still, coating may affect toxicity. The aim of this work was to evaluate the possible effects of oleic acid-coated ION (O-ION) on human neuronal cells (SH-SY5Y). A set of assays was conducted in complete and serum-free culture media for 3 and 24 h to assess O-ION cytotoxic effects - cell membrane disruption, cell cycle alteration and cell death induction -, and genotoxic effects - primary DNA damage, H2AX phosphorylation and micronuclei induction -, considering also DNA repair competence and iron ion release. Results obtained show that O-ION exhibit a moderate cytotoxicity related to cell membrane impairment, cell cycle disruption and cell death induction, especially notable in serum-free medium. Iron ion release was only observed in complete medium, indicating that cytotoxicity observed was not related to the presence of ions in the medium. However, O-ION genotoxic effects were limited to the induction of primary DNA damage, not related to double strand breaks, and this damage did not become fixed in cells in most conditions. Alterations in repair ability (DNA repair competence assay) were observed when cells where treated with O-ION before or during the challenge with H2O2, but not during the repair period. Further investigation is needed to clarify the possible role of oxidative stress and protein corona on observed O-ION toxicity.