Relating Cytotoxicity, Zinc Ions, and Reactive Oxygen in ZnO

Although zinc oxide (ZnO) nanoparticles (NPs) have been widely formulated in sunscreens, the relationship between reac-tive oxygen species (ROS) generation induced by these particles, zinc ions, and cytotoxicity is not clearly understood. This study explores whether these factors can be accurately quantified and related. The study demonstrates a strong correlation between ZnO NP–induced cytotoxicity and free intracellular zinc concentra-tion (R2 = .945) in human immune cells, indicating a requirement for NP dissolution to precede cytotoxicity. In addition, although direct exposure to ZnO NPs was found to induce cytotoxicity at relatively high concentrations, indirect exposure (via dialysis) was not cytotoxic, even at extremely high concentrations, highlighting a requirement for NP-to-cell contact. Elevated levels of ROS pre-sent in NP-exposed cells also correlated to both cytotoxicity and intracellular free zinc. Although the addition of antioxidant wa