In vitro mechanistic study towards a better understanding of ZnO nanoparticle toxicity

Tina Buerki-Thurnherr*a, Lisong Xiaob, Liliane Dienera, Osman Arslanb, Cordula Hirscha, Xenia Maeder-Althausa, Kathrin Griederc, Bruno Wampflerc, Sanjay Mathurb, Peter Wicka & Harald F. Krugaa Empa, Swiss Federal Laboratories for Materials Testing and Technology, Laboratory for Materials-Biology Interactions, Lerchenfeldstrasse, St. Gallen, Switzerlandb Institute of Inorganic Chemistry, University of Cologne, Greinstrasse, Cologne, Germanyc Empa, Swiss Federal Laboratories for Materials Testing and Technology, Laboratory for Biomaterials, Lerchenfeldstrasse, St. Gallen, SwitzerlandCorrespondence: Dr T. Buerki-Thurnherr, Empa, Swiss Federal Laboratories for Materials Testing and Technology, Laboratory for Materials-Biology Interaction, Lerchenfeldstrasse 5, 9014 St. Gallen, Switzerland. +41 58 765 76 96. +41 58 765 76 94. tina.buerki@empa.ch AbstractZnO nanoparticles (NPs) elicit significant adverse effects in various cell types, organisms and in the environment. The toxicity of nanoscale ZnO has often been ascribed to the release of zinc ions from the NPs but it is not yet understood to which extent these ions contribute to ZnO NP toxicity and what are the underlying mechanisms. Here, we take one step forward by demonstrating that ZnO-induced Jurkat cell death is largely an ionic effect involving the extracellular release of high amounts of Zn(II), their rapid uptake by the cells and the induction of a caspase-independent alternative apoptosis pathway that is independent of the formation of ROS. In addition, we identified novel coating strategies to reduce ZnO NP dissolution and subsequent adverse effects.