Copper-Iron Oxide Nanoparticles Induce Apoptosis and Cell Cycle Arrest in Human Airway Epithelial Cells via Oxidative...

Metal oxide nanoparticles are employed in various applications such as medicine, environmental remediation, molecular sensing, and drug delivery. However, large-scale commercial production and the use of smaller-sized nanoparticles increase the potential risk of toxicity to humans. Therefore, there is an urgent need to investigate the toxicity of nanomaterials. This study evaluated the toxic effects of copper-iron oxide nanoparticles (CIONPs) on human airway epithelial HEp-2 cells. The HEp-2 cells were exposed to different concentrations of CIONPs for 24 h. Various toxicological assays were used to assess cytotoxicity (MTT and neutral red assays), morphological changes, oxidative stress (GSH and LPO), ROS production, mitochondrial membrane dysfunction, cell cycle arrest, and mRNA expression of apoptotic marker genes (p53, caspase-3, caspase-9, Bax, and Bcl-2). The results revealed that 24-h exposure to CIONPs caused significant cytotoxicity and morphological damage in HEp-2 cells in a dose-dependent manner. Further cytotoxic doses of CIONPs influenced oxidative stress by decreasing GSH level and increasing LPO and ROS levels in HEp-2 cells. Moreover, exposure to CIONPs induced cell death by diminishing mitochondrial membrane potential and blocking the cell cycle in the SubG1 phase. Furthermore, CIONPs induced apoptosis by upregulating proapoptotic marker genes (p53, caspase-3, caspase-9, and Bax) and downregulating the antiapoptotic gene Bcl-2 in HEp-2 cells. Overall, the results of this study demonstrated that CIONPs are highly toxic to HEp-2 cells, indicating that the airway epithelium is one of the targets of CIONPs toxicity in humans. Therefore, these nanoparticles should be used with appropriate care.