Toxic effects of metal oxide nanoparticles and their underlying mechanisms

Nanomaterials have attracted considerable interest owing to their unique physicochemical properties. The wide application of nanomaterials has raised many concerns about their potential risks to human health and the environment. Metal oxide nanoparticles (MONPs), one of the main members of nanomaterials, have been applied in various fields, such as food, medicine, cosmetics, and sensors. This review highlights the bio-toxic effects of widely applied MONPs and their underlying mechanisms. Two main underlying toxicity mechanisms, reactive oxygen species (ROS)- and non-ROS-mediated toxicities, of MONPs have been widely accepted. ROS activates oxidative stress, which leads to lipid peroxidation and cell membrane damage. In addition, ROS can trigger the apoptotic pathway by activating caspase-9 and -3. Non-ROS-mediated toxicity mechanism includes the effect of released ions, excessive accumulation of NPs on the cell surface, and combination of NPs with specific death receptors. Furthermore, the combined toxicity evaluation of some MONPs is also discussed. Toxicity may dramatically change when nanomaterials are used in a combined system because the characteristics of NPs that play a key role in their toxicity such as size, surface properties, and chemical nature in the complex system are different from the pristine NPs.