Investigation of Cytotoxicity, Apoptosis, and Oxidative Stress Response of Fe3O4-RGO Nanocomposites in Human Liver HepG2 cells

Abstract

Iron oxide–reduced graphene oxide (Fe3O4-RGO) nanocomposites have attracted enormous interest in the biomedical field. However, studies on biological response of Fe3O4-RGO nanocomposites at the cellular and molecular level are scarce. This study was designed to synthesize, characterize, and explore the cytotoxicity of Fe3O4-RGO nanocomposites in human liver (HepG2) cells. Potential mechanisms of cytotoxicity of Fe3O4-RGO nanocomposites were further explored through oxidative stress. Prepared samples were characterized by UV-visible spectrophotometer, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. The results demonstrated that RGO induce dose-dependent cytotoxicity in HepG2 cells. However, Fe3O4-RGO nanocomposites were not toxic. We further noted that RGO induce apoptosis in HepG2 cells, as evidenced by mitochondrial membrane potential loss, higher caspase-3 enzyme activity, and cell cycle arrest. On the other hand, Fe3O4-RGO nanocomposites did not alter these apoptotic parameters. Moreover, we observed that RGO increases intracellular reactive oxygen species and hydrogen peroxide while decrease antioxidant glutathione. Again, Fe3O4-RGO nanocomposites did not exert oxidative stress. Altogether, we found that RGO significantly induced cytotoxicity, apoptosis and oxidative stress. However, Fe3O4-RGO nanocomposites showed good biocompatibility to HepG2 cells. This study warrants further research to investigate the biological response of Fe3O4-RGO nanocomposites at the gene and molecular level.

Cytotoxicity Effect of Iron Oxide (Fe3O4)/Graphene Oxide (GO) Nanosheets in Cultured HBE Cells

“…It has been previously reported by several researchers that ROS [such as superoxide anions (O 2 • − ), hydroxyl radicals (HO•), and hydrogen peroxide] levels could enhance in human cells after exposure to Fe 3 O 4 /GO nanosheets. Literature also unravels that iron oxide nanoparticles can induce cytotoxicity by activating oxidative stress responses ( Ahamed et al, 2020 ). To further detect whether Fe 3 O 4 /GO induces ROS production in HBE cells, DCFH staining was used.…”

“…Nowadays, some of these attractive metal oxides have been documented to be cytotoxic and genotoxic, potentially leading to the destruction of mitochondrial membrane integrity, DNA fragmentation, and cell death ( Li et al, 2018 ). Due to the tremendous potential of Fe 3 O 4 /GO in biomedical and other fields, recent researches have focused on the potential cytotoxicity and genetic toxicity of these hybrids ( Ahamed et al, 2020 ; Zhang H. et al, 2020 ). However, the relationship of Fe 3 O 4 /GO exposure with ROS and calcium ion levels and apoptosis remains enigmatic.…”

Comprehensive Study on the Reinforcement of Electrospun PHB Scaffolds with Composite Magnetic Fe3O4–rGO Fillers: Structure, Physico-Mechanical Properties, and Piezoelectric Response

“…For example, a high Fe 3 O 4 content is effective in improving the osteoconductivity of a Fe 3 O 4 –rGO nanocomposite. 43 Much research has been devoted to the use of composites in the areas of drug loading, 44 separation, and chemical extraction, 30 sensors, and biosensors because of the synergistic effect of the rGO matrix and Fe 3 O 4 , 45 which is aimed at enhancing the conductivity and ionic diffusion, thus giving a material with superior electrochemical performance. Accordingly, Fe 3 O 4 –rGO composites have various promising applications due to a synergistic combination of high saturation magnetization of Fe 3 O 4 with high conductivity and high surface-to-volume ratio of rGO.…”

Effects of Metallic and Carbon-Based Nanomaterials on Human Pancreatic Cancer Cell Lines AsPC-1 and BxPC-3

“…This process was suggested as one of the possible mechanisms underlying carbon-based nanomaterial cytotoxicity [23]. GO was proven to be cytotoxic in doses that exceeded 200 mg/L for the lung cancer cell line A549 [22,24] or the human liver cell line HepG2 [25]. ND are characterized by high rigidity, chemical stability, a large surface area, and a high absorption capacity [26].…”