Toxicity of ZnO Nanoparticles to Macrophages Due to Cell Uptake and Intracellular Release of Zinc Ions

Although the ZnO nanoparticles (NPs) have been widely used in research and industry, their health risks are only concerned very recently. In this paper, attention is paid to elucidate the toxic effects and intrinsic mechanism of ZnO NPs to RAW 246.7 macrophage cells. The ZnO NPs from industry additives had a diameter of ∼37 nm in a dry state and aggregated to submicron size in cell culture medium with slightly negative surface charge. Influences of ZnO NPs on cell toxicity and functions were then studied in terms of cell viability, mitochondrial membrane potential (MMP), total and released lactate dehydrogenase (LDH) activity, intracellular level of reactive oxygen species (ROS) and Zn²⁺ concentration. The ZnO NPs induced elevation of intracellular Zn²⁺ concentration, leading to the over generation of intracellular ROS, leakage of plasma membrane, dysfunction of mitochondria, and cell death. The solubility of ZnO NPs was found largely enhanced in acidic environment (pH 5.5), compared to physiological condition (pH 7.2). Inhibition of cell uptake of ZnO NPs would largely reduce the cytotoxicity. These results demonstrate that the cell uptake, intracellular dissolution and thereafter release of Zn²⁺ are the intrinsic reasons for the high toxicity of ZnO NPs.