Zinc oxide nanoparticles as selective killers of proliferating cells

TY - JOUR

T1 - Zinc oxide nanoparticles as selective killers of proliferating cells

A1 - Taccola,Liuba

A1 - Raffa,Vittoria

A1 - Riggio,Cristina

A1 - Vittorio,Orazio

A1 - Iorio,Maria Carla

A1 - Vanacore,Renato

A1 - Pietrabissa,Andrea

A1 - Cuschieri,Alfred

AU - Taccola,Liuba

AU - Raffa,Vittoria

AU - Riggio,Cristina

AU - Vittorio,Orazio

AU - Iorio,Maria Carla

AU - Vanacore,Renato

AU - Pietrabissa,Andrea

AU - Cuschieri,Alfred

PY - 2011/5

Y1 - 2011/5

N2 - <p>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.</p><p>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.</p><p>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.</p><p>Conclusion: Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant.</p>

AB - <p>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.</p><p>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.</p><p>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.</p><p>Conclusion: Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant.</p>

KW - zinc oxide nanoparticles

KW - dispersion

KW - selective cytotoxicity

KW - mesenchymal stem cells

KW - ZNO NANOPARTICLES

KW - OPTICAL-PROPERTIES

KW - NANOSTRUCTURES

KW - INDUCTION

KW - MECHANISM

KW - AUTOPHAGY

KW - TOXICITY

KW - BACTERIA

KW - MARROW

U2 - 10.2147/IJN.S16581

DO - 10.2147/IJN.S16581

M1 - Article

JO - International Journal of Nanomedicine

JF - International Journal of Nanomedicine

SN - 1178-2013

VL - 6

SP - 1129

EP - 1140

ER -