Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models

Zhizhi Sun,1 Vinith Yathindranath,2 Matthew Worden,3 James A Thliveris,4 Stephanie Chu,1 Fiona E Parkinson,1 Torsten Hegmann,1&ndash;3 Donald W Miller1 1Department of Pharmacology and Therapeutics, 2Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada; 3Chemical Physic...

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Autores principales:	Sun Z, Yathindranath V, Worden M, Thliveris JA, Chu S, Parkinson FE, Hegmann T, Miller DW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/35e4fd3345bd45e9ae6f886f9889588c
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spelling	oai:doaj.org-article:35e4fd3345bd45e9ae6f886f9889588c2021-12-02T05:15:59ZCharacterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models1176-91141178-2013https://doaj.org/article/35e4fd3345bd45e9ae6f886f9889588c2013-03-01T00:00:00Zhttp://www.dovepress.com/characterization-of-cellular-uptake-and-toxicity-of-aminosilane-coated-a12398https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Zhizhi Sun,1 Vinith Yathindranath,2 Matthew Worden,3 James A Thliveris,4 Stephanie Chu,1 Fiona E Parkinson,1 Torsten Hegmann,1&ndash;3 Donald W Miller1 1Department of Pharmacology and Therapeutics, 2Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada; 3Chemical Physics Interdisciplinary Program, Liquid Crystal Institute, Kent State University, Kent, OH, USA; 4Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada&nbsp; Background: Aminosilane-coated iron oxide nanoparticles (AmS-IONPs) have been widely used in constructing complex and multifunctional drug delivery systems. However, the biocompatibility and uptake characteristics of AmS-IONPs in central nervous system (CNS)-relevant cells are unknown. The purpose of this study was to determine the effect of surface charge and magnetic field on toxicity and uptake of AmS-IONPs in CNS-relevant cell types. Methods: The toxicity and uptake profile of positively charged AmS-IONPs and negatively charged COOH-AmS-IONPs of similar size were examined using a mouse brain microvessel endothelial cell line (bEnd.3) and primary cultured mouse astrocytes and neurons. Cell accumulation of IONPs was examined using the ferrozine assay, and cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: No toxicity was observed in bEnd.3 cells at concentrations up to 200 &micro;g/mL for either AmS-IONPs or COOH-AmS-IONPs. AmS-IONPs at concentrations above 200 &micro;g/mL reduced neuron viability by 50% in the presence or absence of a magnetic field, while only 20% reductions in viability were observed with COOH-AmS-IONPs. Similar concentrations of AmS-IONPs in astrocyte cultures reduced viability to 75% but only in the presence of a magnetic field, while exposure to COOH-AmS-IONPs reduced viability to 65% and 35% in the absence and presence of a magnetic field, respectively. Cellular accumulation of AmS-IONPs was greater in all cell types examined compared to COOH-AmS-IONPs. Rank order of cellular uptake for AmS-IONPs was astrocytes &gt; bEnd.3 &gt; neurons. Accumulation of COOH-AmS-IONPs was minimal and similar in magnitude in different cell types. Magnetic field exposure enhanced cellular accumulation of both AmS- and COOH-AmS-IONPs. Conclusion: Both IONP compositions were nontoxic at concentrations below 100 &micro;g/mL in all cell types examined. At doses above 100 &micro;g/mL, neurons were more sensitive to AmS-IONPs, whereas astrocytes were more vulnerable toward COOH-AmS-IONPs. Toxicity appears to be dependent on the surface coating as opposed to the amount of iron-oxide present in the cell. Keywords: drug delivery, magnetic nanoparticles, magnetic field, biocompatibility, cellular accumulation, brainSun ZYathindranath VWorden MThliveris JAChu SParkinson FEHegmann TMiller DWDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 961-970 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Sun Z Yathindranath V Worden M Thliveris JA Chu S Parkinson FE Hegmann T Miller DW Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models
description	Zhizhi Sun,1 Vinith Yathindranath,2 Matthew Worden,3 James A Thliveris,4 Stephanie Chu,1 Fiona E Parkinson,1 Torsten Hegmann,1&ndash;3 Donald W Miller1 1Department of Pharmacology and Therapeutics, 2Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada; 3Chemical Physics Interdisciplinary Program, Liquid Crystal Institute, Kent State University, Kent, OH, USA; 4Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada&nbsp; Background: Aminosilane-coated iron oxide nanoparticles (AmS-IONPs) have been widely used in constructing complex and multifunctional drug delivery systems. However, the biocompatibility and uptake characteristics of AmS-IONPs in central nervous system (CNS)-relevant cells are unknown. The purpose of this study was to determine the effect of surface charge and magnetic field on toxicity and uptake of AmS-IONPs in CNS-relevant cell types. Methods: The toxicity and uptake profile of positively charged AmS-IONPs and negatively charged COOH-AmS-IONPs of similar size were examined using a mouse brain microvessel endothelial cell line (bEnd.3) and primary cultured mouse astrocytes and neurons. Cell accumulation of IONPs was examined using the ferrozine assay, and cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: No toxicity was observed in bEnd.3 cells at concentrations up to 200 &micro;g/mL for either AmS-IONPs or COOH-AmS-IONPs. AmS-IONPs at concentrations above 200 &micro;g/mL reduced neuron viability by 50% in the presence or absence of a magnetic field, while only 20% reductions in viability were observed with COOH-AmS-IONPs. Similar concentrations of AmS-IONPs in astrocyte cultures reduced viability to 75% but only in the presence of a magnetic field, while exposure to COOH-AmS-IONPs reduced viability to 65% and 35% in the absence and presence of a magnetic field, respectively. Cellular accumulation of AmS-IONPs was greater in all cell types examined compared to COOH-AmS-IONPs. Rank order of cellular uptake for AmS-IONPs was astrocytes &gt; bEnd.3 &gt; neurons. Accumulation of COOH-AmS-IONPs was minimal and similar in magnitude in different cell types. Magnetic field exposure enhanced cellular accumulation of both AmS- and COOH-AmS-IONPs. Conclusion: Both IONP compositions were nontoxic at concentrations below 100 &micro;g/mL in all cell types examined. At doses above 100 &micro;g/mL, neurons were more sensitive to AmS-IONPs, whereas astrocytes were more vulnerable toward COOH-AmS-IONPs. Toxicity appears to be dependent on the surface coating as opposed to the amount of iron-oxide present in the cell. Keywords: drug delivery, magnetic nanoparticles, magnetic field, biocompatibility, cellular accumulation, brain
format	article
author	Sun Z Yathindranath V Worden M Thliveris JA Chu S Parkinson FE Hegmann T Miller DW
author_facet	Sun Z Yathindranath V Worden M Thliveris JA Chu S Parkinson FE Hegmann T Miller DW
author_sort	Sun Z
title	Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models
title_short	Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models
title_full	Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models
title_fullStr	Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models
title_full_unstemmed	Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models
title_sort	characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/35e4fd3345bd45e9ae6f886f9889588c
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Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models

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