Role of surface charge and oxidative stress in cytotoxicity and genotoxicity of graphene oxide towards human lung fibroblast cells

Abstract

Recently, attempts have been made to apply graphene oxide (GO) in the field of biology and medicine, such as DNA sensing and drug delivery with some necessary modifications. Therefore, the toxicity of GO must be evaluated before it is applied further in biomedicine. In this paper, the cytotoxicity and genotoxicity of GO to human lung fibroblast (HLF) cells have been assessed with methyl thiazolyl tetrazolium (MTT), sub-G1 measurement and comet assays, and the mechanism of its toxicity has been explored. Various modifications of GO have been made to help us determine the factors which could affect the toxicity of GO. The results indicated that cytotoxicity and genotoxicity of GO to HLF cells were concentration dependent, and the genotoxicity induced by GO was more severe than the cytotoxicity to HLF cells. Oxidative stress mediated by GO might explain the reason of its toxic effect. Furthermore, the electronic charge on the surface of GO would play a very important role in the toxicity of GO to HLF cells.

Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule

“…60 Previous studies have indicated that the interaction of nanoparticles with the cell membrane triggered ROS generation and oxidative stress, which may cause breakdown of membrane lipids, alterations in metabolic pathways, and apoptosis. 88,90,91 The increase in ROS production by GO and RES-rGO is in agreement with the results of the WST-8 and LDH assays, suggesting that GO and RES-rGO induce cytotoxicity via oxidative stress. Reddy et al 92 have shown that multi-walled carbon nanotubes induce oxidative stress-dependent cytotoxicity in cultured human embryonic kidney cells.…”

“…The treatment with RES-rGO and H-rGO caused a more pronounced negative effect on the membrane integrity of A2780 cells than GO, indicating enhanced cytotoxicity, whereas RES-rGO and H-rGO show significant leakage. Zhang et al 83 have reported that graphene aggregation induced LDH leakage in rat pheochromocytoma PC12 cells, while Wang et al 88 have demonstrated that GO caused cytotoxicity and genotoxicity in human lung fibroblast cells, which correlated with its effects on cell membrane integrity and depended on particle size, shape, composition, and surface charge and chemistry.…”

Exceedingly biocompatible and thin-layered reduced graphene oxide nanosheets using an eco-friendly mushroom extract strategy

“…GO ( Figure 9C) showed obvious toxicity towards MRC-5 as compared to the untreated cells, even from concentrations as low as 5 μg/mL. A previous investigation by Wang et al 82 supports this observation, where GO was found to induce cytotoxicity, genotoxicity, and oxidative stress to MRC-5 cells. In contrast, RGO showed no cytotoxicity towards normal cell lines with the cell viability above 90%, even at 50 μg/mL.…”

Toxicity studies of six types of carbon nanoparticles in a chicken-embryo model

“…They also hypothesized that positively charged particles might disrupt the charge balance of the cell membrane and induce cell damage at a later stage, while negatively charged NPs have an inferior rate of endocytosis and do not utilize the clathrin-mediated endocytosis pathway. 50 The results from our study did not identify such correlations among the CNPs investigated, either with regard to positive/negative charge or ζ-potential. This indicates that the key toxicological factor may depend on another parameter, such as the identity of functional groups on the CNP structures.…”

“…According to Wang et al, 50 the higher ζ-potential of GO and GO derivatives causes more severe cell damage, but when the level of charge on its surface was high enough, charge did not directly correlate with toxicity. They also hypothesized that positively charged particles might disrupt the charge balance of the cell membrane and induce cell damage at a later stage, while negatively charged NPs have an inferior rate of endocytosis and do not utilize the clathrin-mediated endocytosis pathway.…”