title: Zinc oxide nanoparticles as selective killers of proliferating cells.
abstract: BACKGROUND
  It has recently been demonstrated that zinc oxide nanoparticles (ZnO NPs) induce death of cancerous cells whilst having no cytotoxic effect on normal cells. However, there are several issues which need to be resolved before translation of zinc oxide nanoparticles into medical use, including lack of suitable biocompatible dispersion protocols and a better understanding being needed of the mechanism of their selective cytotoxic action.
  
  
  METHODS
  Nanoparticle dose affecting cell viability was evaluated in a model of proliferating cells both experimentally and mathematically. The key issue of selective toxicity of ZnO NPs toward proliferating cells was addressed by experiments using a biological model of noncancerous cells, ie, mesenchymal stem cells before and after cell differentiation to the osteogenic lineage.
  
  
  RESULTS
  In this paper, we report a biocompatible protocol for preparation of stable aqueous solutions of monodispersed zinc oxide nanoparticles. We found that the threshold of intracellular ZnO NP concentration required to induce cell death in proliferating cells is 0.4 ± 0.02 mM. Finally, flow cytometry analysis revealed that the threshold dose of zinc oxide nanoparticles was lethal to proliferating pluripotent mesenchymal stem cells but exhibited negligible cytotoxic effects to osteogenically differentiated mesenchymal stem cells.
  
  
  CONCLUSIONS
  Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant.
authors.affiliation: Department of Oncology, Transplantation and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy.
authors.forename: Liuba
authors.initials: L
authors.lastname: Taccola
authors.forename: Vittoria
authors.initials: V
authors.lastname: Raffa
authors.forename: Cristina
authors.initials: C
authors.lastname: Riggio
authors.forename: Orazio
authors.initials: O
authors.lastname: Vittorio
authors.forename: Maria Carla
authors.initials: MC
authors.lastname: Iorio
authors.forename: Renato
authors.initials: R
authors.lastname: Vanacore
authors.forename: Andrea
authors.initials: A
authors.lastname: Pietrabissa
authors.forename: Alfred
authors.initials: A
authors.lastname: Cuschieri
mesh_terms: D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020342:Finite Element Analysis; D005434:Flow Cytometry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D051381:Rats; D011920:Rats, Inbred WF; D017382:Reactive Oxygen Species / Q000378:metabolism; D013052:Spectrometry, X-Ray Emission; D013778:Tetrazolium Salts; D013844:Thiazoles; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D015034:Zinc Oxide