Free zinc ions, as a major factor of ZnONP toxicity, disrupts free radical homeostasis in CCRF-CEM cells.

Nanotechnology has become a ubiquitous part of our everyday life. Besides the already-known nanoparticles (NPs), plenty of new nanomaterials are being synthesized every day. Here, we explain the mechanism of the zinc oxide nanoparticles (ZnONPs) cytotoxicity in a cellular model of acute lymphoblastic leukaemia (CCRF-CEM). To do so, we investigated both possible hypotheses about the ZnONPs mechanism of toxicity: a free zinc ions release and/or reactive oxygen species (ROS) generation. Presented here results show that: Our results support the hypothesis that the mechanism of ZnONPs cytotoxicity is based on the release of free zinc ions. Nevertheless, both previously quoted hypotheses incompletely described the mechanism of action of ZnONPs. In this paper, we show that the mechanism of cytotoxicity of ZnONPs is based on the induction of reductive stress in CCRF-CEM cells, which is caused by free zinc ions released from ZnONPs. Therefore, the increase of oxidative stress markers is most likely a secondary response of the cells towards the Zn. These results provide a crucial expansion of the zinc ion hypothesis and thus explain the biphasic cellular response of CCRF-CEM cells treated with ZnONPs.