Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles

Abstract

Surface coatings of nanoparticles (NPs) are known to influence advantageous features of NPs as well as potential toxicity. Iron oxide (Fe3O4) NPs are applied for both medical diagnostics and targeted drug delivery. We investigated the potential cytotoxicity and genotoxicity of uncoated iron oxide (U-Fe3O4) NPs in comparison with oleate-coated iron oxide (OC-Fe3O4) NPs. Testing was performed in vitro in human lymphoblastoid TK6 cells and in primary human blood cells. For cytotoxicity testing, relative growth activity, trypan blue exclusion, (3)H-thymidine incorporation and cytokinesis-block proliferation index were assessed. Genotoxicity was evaluated by the alkaline comet assay for detection of strand breaks and oxidized purines. Particle characterization was performed in the culture medium. Cellular uptake, morphology and pathology were evaluated by electron microscopy. U-Fe3O4 NPs were found not to be cytotoxic (considering interference of NPs with proliferation test) or genotoxic under our experimental conditions. In contrast, OC-Fe3O4 NPs were cytotoxic in a dose-dependent manner, and also induced DNA damage, indicating genotoxic potential. Intrinsic properties of sodium oleate were excluded as a cause of the toxic effect. Electron microscopy data were consistent with the cytotoxicity results. Coating clearly changed the behaviour and cellular uptake of the NPs, inducing pathological morphological changes in the cells.

Nanomaterials - a New and Former Public Health Issue. The Case of Slovakia

“…Within the project, CPIA periodically organizes conferences and other specialized actions aimed at responsible use of nanomaterials (24,25). One member of staff from the Centre for Chemical Substances and Preparations of the Ministry of Economy has participated in the creation of EU legislation in the field of chemicals including nanomaterials (26), as a member of the Nanomaterial Working Group of European Chemical Agency (ECHA-NMWG) and Competent Authorities Sub-Group on Nanomaterials (CASG Nano-REACH). One employee of the Ministry of the Environment is dedicated to nanosafety as a member of the Working Party on Manufactured Nanomaterials of the Organisation for Economic Cooperation and Development (OECD).…”

Toxicological evaluation of dextran stabilized iron oxide nanoparticles in human peripheral blood lymphocytes

“…Cytotoxicity analysis showed that the frequencies of viable, early apoptotic and late apoptotic/necrotic cells were not affected by DIONPs at any of the 35 Similarly, NP size-dependent and surface coating-dependent toxicity effects were reported in human T-lymphocyte. 36 In a comparative study involving different NPs, iron oxide NPs were shown to decrease cell viability and induce oxidative stress and DNA damage.…”

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

“…27 Another study explored the effects of bare or oleate-covered IONPs on human lymphoblastoid TK6 cells and primary blood cells. 17 Surprisingly, oleate-coated IONPs possessed dose-dependent cyto-and genotoxicity whereas bare IONPs were nontoxic at the equivalent dose. Our results clearly indicate that the presence of either silica core or silica shell substantially increases the toxicity of IONPs.…”

“…17 Although oleate itself was not found to be cytotoxic, it somehow modified the internalization of nanoparticles and cellular response to IONP accumulation. Silica coating is commonly used to passivate IONPs; 18,19 however, at present it is not known whether the presence of silica core or silica nanoflakes in the composite IONPs will affect their cytotoxicity.…”