Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles
Igor M Pongrac,1 Ivan Pavičić,2 Mirta Milić,2 Lada Brkič Ahmed,1 Michal Babič,3 Daniel Horák,3 Ivana Vinković Vrček,2 Srećko Gajović1 1School of Medicine, Croatian Institute for Brain Research, University of Zagreb, 2Institute for Medical Research and Occupational Health, Zagreb, Croatia...
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Dove Medical Press
2016
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oai:doaj.org-article:86ff04ff7c914adfb11c022eb1de2e1b2021-12-02T00:30:22ZOxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles1178-2013https://doaj.org/article/86ff04ff7c914adfb11c022eb1de2e1b2016-04-01T00:00:00Zhttps://www.dovepress.com/oxidative-stress-response-in-neural-stem-cells-exposed-to-different-su-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Igor M Pongrac,1 Ivan Pavičić,2 Mirta Milić,2 Lada Brkič Ahmed,1 Michal Babič,3 Daniel Horák,3 Ivana Vinković Vrček,2 Srećko Gajović1 1School of Medicine, Croatian Institute for Brain Research, University of Zagreb, 2Institute for Medical Research and Occupational Health, Zagreb, Croatia; 3Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic Abstract: Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs) are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs – uncoated, coated with D-mannose, or coated with poly-L-lysine – affects biocompatibility. We sought to investigate murine neural stem cells (NSCs) as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions presented in this work highlights the need for further safety evaluations. This investigation helps to fill the knowledge gaps on the criteria that should be considered in evaluating the biocompatibility and safety of novel nanoparticles. Keywords: superparamagnetic iron oxide nanoparticles, biocompatibility, oxidative stress, genotoxicity, murine neural stem cellsPongrac IMPavičić IMilić MBrkić Ahmed LBabič MHorák DVinković Vrček IGajović SDove Medical Pressarticlesuperparamagnetic iron oxide nanoparticlesbiocompatibilityoxidative stressgenotoxicitymurine neural stem cellsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1701-1715 (2016) |
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superparamagnetic iron oxide nanoparticles biocompatibility oxidative stress genotoxicity murine neural stem cells Medicine (General) R5-920 |
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superparamagnetic iron oxide nanoparticles biocompatibility oxidative stress genotoxicity murine neural stem cells Medicine (General) R5-920 Pongrac IM Pavičić I Milić M Brkić Ahmed L Babič M Horák D Vinković Vrček I Gajović S Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles |
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Igor M Pongrac,1 Ivan Pavičić,2 Mirta Milić,2 Lada Brkič Ahmed,1 Michal Babič,3 Daniel Horák,3 Ivana Vinković Vrček,2 Srećko Gajović1 1School of Medicine, Croatian Institute for Brain Research, University of Zagreb, 2Institute for Medical Research and Occupational Health, Zagreb, Croatia; 3Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic Abstract: Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs) are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs – uncoated, coated with D-mannose, or coated with poly-L-lysine – affects biocompatibility. We sought to investigate murine neural stem cells (NSCs) as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions presented in this work highlights the need for further safety evaluations. This investigation helps to fill the knowledge gaps on the criteria that should be considered in evaluating the biocompatibility and safety of novel nanoparticles. Keywords: superparamagnetic iron oxide nanoparticles, biocompatibility, oxidative stress, genotoxicity, murine neural stem cells |
format |
article |
author |
Pongrac IM Pavičić I Milić M Brkić Ahmed L Babič M Horák D Vinković Vrček I Gajović S |
author_facet |
Pongrac IM Pavičić I Milić M Brkić Ahmed L Babič M Horák D Vinković Vrček I Gajović S |
author_sort |
Pongrac IM |
title |
Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles |
title_short |
Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles |
title_full |
Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles |
title_fullStr |
Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles |
title_full_unstemmed |
Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles |
title_sort |
oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles |
publisher |
Dove Medical Press |
publishDate |
2016 |
url |
https://doaj.org/article/86ff04ff7c914adfb11c022eb1de2e1b |
work_keys_str_mv |
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