Cytotoxicity and genotoxicity of iron oxide nanoparticles: An in vitro biosafety study

Abstract

With the development of nanotechnology and the wide use of iron oxide nanoparticles, it has become necessary to assess the potential adverse biological effects of magnetite. This study investigated the cytotoxicity, genotoxicity and oxidative damage of different concentrations of magnetite (0 to 1000 mg/L) in human whole blood cultures. After supplementation of magnetite, the blood samples were incubated for 72 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays. The total antioxidant capacity (TAC) and total oxidant status (TOS) were determined to evaluate the dose-dependent effects of magnetite on the oxidant/antioxidant balance and to evaluate the potential oxidative injury due to increased oxidative stress. Genotoxicity was estimated by by the sister chromatid exchange (SCE), micronuclei (MN) and chromosome aberration (CA) assays and determination of 8-oxo-2-deoxyguanosine (8-OH-dG) levels. The results of MTT and LDH assays showed that the higher concentrations of magnetite (100, 150, 300, 500 and 1000 mg/L) decreased cell viability. Concentrations of magnetite higher than 10 mg/L increased TOS levels and decreased TAC levels in human blood cells. Increasing concentrations of magnetite caused significant increases in MN, SCE and CA rates and 8-OH-dG levels. The obtained results showed that magnetite exerted dose-dependent effects on oxidative damage, genotoxicity and cytotoxicity in human blood cells.

Iron Oxide Nanoparticles for Biomedical Applications: A Perspective on Synthesis, Drugs, Antimicrobial Activity, and Toxicity

“…Conflicting evidence regarding the toxicity of IONPs has been reported in in vitro and in vivo studies [ 213 , 214 , 215 , 216 ]. Factors inherent to nanosystems involving IONPs tend to directly interfere with their toxicity.…”

“…Positively charged IONPs were shown to be more toxic, since they undergo nonspecific interactions and adsorptive endocytosis with the negatively charged cell membrane, thus increasing their intracellular accumulation and affecting cell membrane integrity [ 218 ]. Other factors such as concentration, type of coating, form of administration, as well as the cell line may explain the different results for IONPs toxicity [ 21 , 22 , 23 , 25 , 26 , 66 , 71 , 72 , 96 , 97 , 98 , 163 , 214 , 215 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 ], as shown in Table 1 .…”

Evaluation of DNA interaction, genotoxicity and oxidative stress induced by iron oxide nanoparticles both in vitro and in vivo: attenuation by thymoquinone

“…16 have also reported that magnetic IONPs cause cellular cytotoxicity to rat lymphocytes via ROS generation in a dose and time-dependent manner 16 . It was also reported that IONPs induced oxidative stress and decreased cell viability of human hepatocytes and human lymphocytes 13,38 . Our study also reported that the exposure of IONPs to rat lymphocytes reduced cell viability in a dose-dependent manner after 24 h, and at the highest concentration (800 μg/ml), the cell viability decreased up to 3 folds.…”

“…The previous studies related to toxicity of IONPs have created a lot of ambiguities 39 . An increase in micronucleus frequency was observed in human peripheral blood after IONPs exposure in a dose-dependent manner 38 . Similarly, oxidative stress-induced DNA damage was also observed after an intraperitoneal administration of IONPs in mice 18,40 .…”

Promotion through external magnetic field of osteogenic differentiation potential in adipose‐derived mesenchymal stem cells: Design of polyurethane/poly(lactic) acid sponges doped with iron oxide nanoparticles

“…The study performed by Kouchesfehani, Kiani, Rostami, and Fakheri () demonstrated that IONP cytotoxicity was mainly dose‐dependent and a concentration of 10 μg/ml already reduced the proliferative activity of mouse embryonic stem cells. Conflicting data exist regarding the cytotoxicity of IONPs (Sonmez et al, ) , (Xu et al, ). It has been shown that not only the dose but also nanoparticle size and shape play an important role in cell toxicity (Lee et al, ).…”