title: In vitro mechanistic study towards a better understanding of ZnO nanoparticle toxicity.
abstract: ZnO 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.
authors.affiliation: Empa, Swiss Federal Laboratories for Materials Testing and Technology, Laboratory for Materials-Biology Interactions, Lerchenfeldstrasse, St. Gallen, Switzerland. tina.buerki@empa.ch
authors.forename: Tina
authors.initials: T
authors.lastname: Buerki-Thurnherr
authors.forename: Lisong
authors.initials: L
authors.lastname: Xiao
authors.forename: Liliane
authors.initials: L
authors.lastname: Diener
authors.forename: Osman
authors.initials: O
authors.lastname: Arslan
authors.forename: Cordula
authors.initials: C
authors.lastname: Hirsch
authors.forename: Xenia
authors.initials: X
authors.lastname: Maeder-Althaus
authors.forename: Kathrin
authors.initials: K
authors.lastname: Grieder
authors.forename: Bruno
authors.initials: B
authors.lastname: Wampfler
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mathur
authors.forename: Peter
authors.initials: P
authors.lastname: Wick
authors.forename: Harald F
authors.initials: HF
authors.lastname: Krug
mesh_terms: D020169:Caspases / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D017382:Reactive Oxygen Species; D015034:Zinc Oxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D020169:Caspases; D015034:Zinc Oxide