Silica coated iron oxide nanoparticles-induced cytotoxicity, genotoxicity and its underlying mechanism in human HK-2 renal proximal tubule epithelial cells.

Autor: Královec K; Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice 532 10, Czech Republic. Electronic address: karel.kralovec@upce.cz., Havelek R; Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, Hradec Králové 500 03, Czech Republic., Kročová E; Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice 532 10, Czech Republic., Kučírková L; Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice 532 10, Czech Republic., Hauschke M; Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, Pardubice 532 10, Czech Republic., Bartáček J; Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic., Palarčík J; Institute of Environmental and Chemical Engineering, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic., Sedlák M; Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic.
Jazyk: angličtina
Zdroj: Mutation research. Genetic toxicology and environmental mutagenesis [Mutat Res Genet Toxicol Environ Mutagen] 2019 Aug; Vol. 844, pp. 35-45. Date of Electronic Publication: 2019 May 30.
DOI: 10.1016/j.mrgentox.2019.05.015
Abstrakt: Iron oxide nanoparticles (IONPs) have a great potential with regard to cell labelling, cell tracking, cell separation, magnetic resonance imaging, magnetic hyperthermia, targeted drug and gene delivery. However, a growing body of research has raised concerns about the possible unwanted adverse cytotoxic effects of IONPs. In the present study, the in vitro cellular uptake, antiproliferative activity, cytotoxicity, genotoxicity, prooxidant, microtubule-disrupting and apoptosis-inducing effect of Fe 3 O 4 @SiO 2 and passivated Fe 3 O 4 @SiO 2 -NH 2 nanoparticles on human renal proximal tubule epithelial cells (HK-2) have been studied. Both investigated silica coated IONPs were found to have cell growth-inhibitory activity in a time- and dose-dependent manner. Determination of cell cycle phase distribution by flow cytometry demonstrated a G1 and G2/M phase accumulation of HK-2 cells. A tetrazolium salt cytotoxicity assay at 24 h following treatment demonstrated that cell viability was reduced in a dose-dependent manner. Microscopy observations showed that both Fe 3 O 4 @SiO 2 and Fe 3 O 4 @SiO 2 -NH 2 nanoparticles accumulated in cells and appeared to have microtubule-disrupting activity. Our study also revealed that short term 1 h exposure to 25 and 100 μg/mL of silica coated IONPs causes genotoxicity. Compared with vehicle control cells, a significantly higher amount of γH2AX foci correlating with an increase in DNA double-strand breaks was observed in Fe 3 O 4 @SiO 2 and Fe 3 O 4 @SiO 2 -NH 2 -treated and immunestained HK-2 cells. The investigated nanoparticles did not trigger significant ROS generation and apoptosis-mediated cell death. In conclusion, these findings provide new insights into the cytotoxicity of silica coated IONPs that may support their further safer use.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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