Copper doping enhanced the oxidative stress-mediated cytotoxicity of TiO₂ nanoparticles in A549 cells

Physicochemical properties of titanium dioxide nanoparticles (TiO₂ NPs) can be tuned by doping with metals or nonmetals. Copper (Cu) doping improved the photocatalytic behavior of TiO₂ NPs that can be applied in various fields such as environmental remediation and nanomedicine. However, interaction of Cu-doped TiO₂ NPs with human cells is scarce. This study was designed to explore the role of Cu doping in cytotoxic response of TiO₂ NPs in human lung epithelial (A549) cells. Characterization data demonstrated the presence of both TiO₂ and Cu in Cu-doped TiO₂ NPs with high-quality lattice fringes without any distortion. The size of Cu-doped TiO₂ NPs (24 nm) was lower than pure TiO₂ NPs (30 nm). Biological results showed that both pure and Cu-doped TiO₂ NPs induced cytotoxicity and oxidative stress in a dose-dependent manner. Low mitochondrial membrane potential and higher caspase-3 enzyme (apoptotic markers) activity were also observed in A549 cells exposed to pure and Cu-doped TiO₂ NPs. We further observed that cytotoxicity caused by Cu-doped TiO₂ NPs was higher than pure TiO₂ NPs. Moreover, antioxidant N-acetyl cysteine effectively prevented the reactive oxygen species generation, glutathione depletion, and cell viability reduction caused by Cu-doped TiO₂ NPs. This is the first report showing that Cu-doped TiO₂ NPs induced cytotoxicity and oxidative stress in A549 cells. This study warranted further research to explore the role of Cu doping in toxicity mechanisms of TiO₂ NPs.