An in vitro study of bare and poly(ethylene glycol)-co-fumarate-coated superparamagnetic iron oxide nanoparticles: a new toxicity identification procedure

As the use of superparamagnetic iron oxide nanoparticles (SPION) in biomedical applications increases (e.g. for targeting drug delivery and imaging), patients are likely to be exposed to products containing SPION. Despite their high biomedical importance, toxicity data for SPION are limited to date. The aim of this study is to investigate the cytotoxicity of SPION and its ability to change cell medium components. Bare and poly(ethylene glycol)-co-fumarate (PEGF)-coated SPION with narrow size distributions were synthesized. The particles were prepared by co-precipitation using ferric and ferrous salts with a molar Fe³⁺/Fe²⁺ ratio of 2. Dulbecco's modified Eagle's medium (DMEM) and primary mouse fibroblast (L929) cell lines were exposed to the SPION. Variation of cell medium components and cytotoxicity due to the interactions with nanoparticles were analyzed using ultraviolet and visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay methods, respectively. The toxicity amount has been traditionally identified by changes in pH and composition in cells and DMEM due to the tendency of SPION to adsorb proteins, vitamins, amino acids and ions. For in vitro toxicity assessments, a new surface passivation procedure is proposed which can yield more reliable quantitative results. It is shown that a more reliable way of identifying cytotoxicity for in vitro assessments is to use particles with saturated surfaces via interactions with DMEM before usage.