In vitro toxicity of FemOn, FemOn-SiO2 composite, and SiO2-FemOn core-shell magnetic nanoparticles

Yana G Toropova,1 Alexey S Golovkin,2 Anna B Malashicheva,3,4 Dmitry V Korolev,5,6 Andrey N Gorshkov,7 Kamil G Gareev,8 Michael V Afonin,9 Michael M Galagudza10,11 1Laboratory of Cardioprotection, Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russian Federation; 2Gene and Cell Engineering Group, Institute of Molecular Biology and Genetics, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russian Federation; 3Laboratory of Molecular Cardiology, Institute of Molecular Biology and Genetics, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russian Federation; 4Department of Embryology, Faculty of Biology, Saint Petersburg State University, Saint Petersburg, Russian Federation; 5Laboratory of Nanotechnology, Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russian Federation; 6Department of Photonics and Optical Information Technology ITMO University, Saint Petersburg, Russian Federation; 7Laboratory of Intracellular Signaling and Transport Research Institute of Influenza, Saint Petersburg, Russian Federation; 8Department of Micro and Nanoelectronics, Faculty of Electronics, Saint Petersburg Electrotechnical University LETI, Saint Petersburg, Russian Federation; 9Department of Inorganic Chemistry Saint Petersburg State Technological Institute (Technical University), Saint Petersburg, Russian Federation; 10Institute of Experimental Medicine, Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russian Federation; 11Departament of Pathophysiology, First Pavlov State Medical University of Saint Petersburg, Saint Petersburg, Russian Federation Abstract: Over the last decade, magnetic iron oxide nanoparticles (IONPs) have drawn much attention for their potential biomedical applications. However, serious in vitro and in vivo safety concerns continue to exist. In this study, the effects of uncoated, FemOn-SiO2 composite flake-like, and SiO2-FemOn core-shell IONPs on cell viability, function, and morphology were tested 48 h postincubation in human umbilical vein endothelial cell culture. Cell viability and apoptosis/necrosis rate were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin V-phycoerythrin kit, respectively. Cell morphology was evaluated using bright-field microscopy and forward and lateral light scattering profiles obtained with flow cytometry analysis. All tested IONP types were used at three different doses, that is, 0.7, 7.0, and 70.0 µg. Dose-dependent changes in cell morphology, viability, and apoptosis rate were shown. At higher doses, all types of IONPs caused formation of binucleated cells suggesting impaired cytokinesis. FemOn-SiO2 composite flake-like and SiO2-FemOn core-shell IONPs were characterized by similar profile of cytotoxicity, whereas bare IONPs were shown to be less toxic. The presence of either silica core or silica nanoflakes in composite IONPs can promote cytotoxic effects. Keywords: iron oxide nanoparticles, composite nanoparticles, silica coating, silica nanoflakes, cytotoxicit