Zinc oxide nanoparticles as selective killers of proliferating cells

Liuba Taccola1, Vittoria Raffa2, Cristina Riggio2, Orazio Vittorio1,2, Maria Carla Iorio3, Renato Vanacore3, Andrea Pietrabissa4,5, Alfred Cuschieri21Department of Oncology, Transplantation and Advanced Technologies in Medicine, University of Pisa, Pisa; 2Medical Science Laboratory, Scuola Superiore...

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Autores principales:	Taccola L, Raffa V,&nbsp;Riggio C, Vittorio O, Iorio MC, Vanacore R, Pietrabissa A, Cuschieri A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8ac1187afcf7429e9f00af859f3e578d
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spelling	oai:doaj.org-article:8ac1187afcf7429e9f00af859f3e578d2021-12-02T04:52:23ZZinc oxide nanoparticles as selective killers of proliferating cells1176-91141178-2013https://doaj.org/article/8ac1187afcf7429e9f00af859f3e578d2011-05-01T00:00:00Zhttp://www.dovepress.com/zinc-oxide-nanoparticles-as-selective-killers-of-proliferating-cells-a7549https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Liuba Taccola1, Vittoria Raffa2, Cristina Riggio2, Orazio Vittorio1,2, Maria Carla Iorio3, Renato Vanacore3, Andrea Pietrabissa4,5, Alfred Cuschieri21Department of Oncology, Transplantation and Advanced Technologies in Medicine, University of Pisa, Pisa; 2Medical Science Laboratory, Scuola Superiore Sant&#39;Anna, Pisa; 3Laboratory of Immunogenetics, Immunohematology, Azienda Ospedaliera Universitaria Pisana, Pisa; 4Department of Surgical Science, Reanimation and Transplantation, University of Pavia, Pavia; 5Fondazione Policlinico San Matteo, Pavia, ItalyBackground: 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 &plusmn; 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.Conclusion: Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant.Keywords: zinc oxide nanoparticles, dispersion, selective cytotoxicity, mesenchymal stem cellsTaccola LRaffa V,&nbsp;Riggio CVittorio OIorio MCVanacore RPietrabissa ACuschieri ADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 1129-1140 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Taccola L Raffa V,&nbsp;Riggio C Vittorio O Iorio MC Vanacore R Pietrabissa A Cuschieri A Zinc oxide nanoparticles as selective killers of proliferating cells
description	Liuba Taccola1, Vittoria Raffa2, Cristina Riggio2, Orazio Vittorio1,2, Maria Carla Iorio3, Renato Vanacore3, Andrea Pietrabissa4,5, Alfred Cuschieri21Department of Oncology, Transplantation and Advanced Technologies in Medicine, University of Pisa, Pisa; 2Medical Science Laboratory, Scuola Superiore Sant&#39;Anna, Pisa; 3Laboratory of Immunogenetics, Immunohematology, Azienda Ospedaliera Universitaria Pisana, Pisa; 4Department of Surgical Science, Reanimation and Transplantation, University of Pavia, Pavia; 5Fondazione Policlinico San Matteo, Pavia, ItalyBackground: 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 &plusmn; 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.Conclusion: Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant.Keywords: zinc oxide nanoparticles, dispersion, selective cytotoxicity, mesenchymal stem cells
format	article
author	Taccola L Raffa V,&nbsp;Riggio C Vittorio O Iorio MC Vanacore R Pietrabissa A Cuschieri A
author_facet	Taccola L Raffa V,&nbsp;Riggio C Vittorio O Iorio MC Vanacore R Pietrabissa A Cuschieri A
author_sort	Taccola L
title	Zinc oxide nanoparticles as selective killers of proliferating cells
title_short	Zinc oxide nanoparticles as selective killers of proliferating cells
title_full	Zinc oxide nanoparticles as selective killers of proliferating cells
title_fullStr	Zinc oxide nanoparticles as selective killers of proliferating cells
title_full_unstemmed	Zinc oxide nanoparticles as selective killers of proliferating cells
title_sort	zinc oxide nanoparticles as selective killers of proliferating cells
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/8ac1187afcf7429e9f00af859f3e578d
work_keys_str_mv	AT taccolal zincoxidenanoparticlesasselectivekillersofproliferatingcells AT raffavampnbspriggioc zincoxidenanoparticlesasselectivekillersofproliferatingcells AT vittorioo zincoxidenanoparticlesasselectivekillersofproliferatingcells AT ioriomc zincoxidenanoparticlesasselectivekillersofproliferatingcells AT vanacorer zincoxidenanoparticlesasselectivekillersofproliferatingcells AT pietrabissaa zincoxidenanoparticlesasselectivekillersofproliferatingcells AT cuschieria zincoxidenanoparticlesasselectivekillersofproliferatingcells
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Zinc oxide nanoparticles as selective killers of proliferating cells

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