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Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice

BACKGROUND: Single wall carbon nanotubes (SWCNTs) are considered promising nanoparticles for industrial and biomedical applications; however their potential toxicity in several biological systems, including the feto-placental unit, has been demonstrated. Functionalization of SWCNTs with polyethylene...

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Autores principales: Campagnolo, Luisa, Massimiani, Micol, Palmieri, Graziana, Bernardini, Roberta, Sacchetti, Cristiano, Bergamaschi, Antonio, Vecchione, Lucia, Magrini, Andrea, Bottini, Massimo, Pietroiusti, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679973/
https://www.ncbi.nlm.nih.gov/pubmed/23742083
http://dx.doi.org/10.1186/1743-8977-10-21
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author Campagnolo, Luisa
Massimiani, Micol
Palmieri, Graziana
Bernardini, Roberta
Sacchetti, Cristiano
Bergamaschi, Antonio
Vecchione, Lucia
Magrini, Andrea
Bottini, Massimo
Pietroiusti, Antonio
author_facet Campagnolo, Luisa
Massimiani, Micol
Palmieri, Graziana
Bernardini, Roberta
Sacchetti, Cristiano
Bergamaschi, Antonio
Vecchione, Lucia
Magrini, Andrea
Bottini, Massimo
Pietroiusti, Antonio
author_sort Campagnolo, Luisa
collection PubMed
description BACKGROUND: Single wall carbon nanotubes (SWCNTs) are considered promising nanoparticles for industrial and biomedical applications; however their potential toxicity in several biological systems, including the feto-placental unit, has been demonstrated. Functionalization of SWCNTs with polyethylene glycol chains (PEG-SWCNTs) dramatically reduces their toxicity, and for this reason PEG-SWCNTs are candidates for biomedical applications. However, no data are available on their safety for the developing embryo, in spite of the clinical and social relevance of this topic. The purpose of this study is therefore to investigate the safety of PEG-SWCNTs for their use as biomedical carriers in pregnancy. METHODS: For toxicological studies, amino-functionalized PEG-SWCNT were intravenously injected in CD1 pregnant mice at different doses (range 0.1-30 μg/mouse), in single or multiple administrations. For biodistribution studies, fluorescently labeled PEG-SWCNTs were obtained by acylation of terminal PEG amino groups with near infrared emitting fluorochromes (PEG-SWCNT-750) and injected at the dosage of 10 μg/mouse, at either day 5.5 (when the placenta is still developing) or day 14.5 of gestation (when the maturation of the placenta is complete). RESULTS: We found no adverse effects both on embryos and dams up to the dose of 10 μg/mouse. At the dose of 30 μg/mouse, occasional teratogenic effects, associated with placental damage, were detected both when administered as a single bolus (1 out of 10 dams; 1 malformed embryo) or as multiple doses (2 out of 10 dams; 5 malformed embryos). The difference in the prevalence of dams with malformed embryos between the 30 μg exposed group and controls approached the statistical significance (p = 0.06). Hepatic damage in dams was seen only in the multiple exposure group (4 out of 10; p = 0.04 when compared with the single exposure group or controls). PEG-SWCNT-750 reached the conceptus when administered early in pregnancy. At later stages, PEG-SWCNT-750 were detected in the placenta and the yolk sac, but not in the embryo. CONCLUSIONS: PEG-SWCNTs may cause occasional teratogenic effects in mice beyond a threshold dose. Such effect might depend on their ability to reach the feto-placenta unit. Although not automatically transferable to humans, these data should be considered if exposing women during pregnancy.
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spelling pubmed-36799732013-06-13 Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice Campagnolo, Luisa Massimiani, Micol Palmieri, Graziana Bernardini, Roberta Sacchetti, Cristiano Bergamaschi, Antonio Vecchione, Lucia Magrini, Andrea Bottini, Massimo Pietroiusti, Antonio Part Fibre Toxicol Research BACKGROUND: Single wall carbon nanotubes (SWCNTs) are considered promising nanoparticles for industrial and biomedical applications; however their potential toxicity in several biological systems, including the feto-placental unit, has been demonstrated. Functionalization of SWCNTs with polyethylene glycol chains (PEG-SWCNTs) dramatically reduces their toxicity, and for this reason PEG-SWCNTs are candidates for biomedical applications. However, no data are available on their safety for the developing embryo, in spite of the clinical and social relevance of this topic. The purpose of this study is therefore to investigate the safety of PEG-SWCNTs for their use as biomedical carriers in pregnancy. METHODS: For toxicological studies, amino-functionalized PEG-SWCNT were intravenously injected in CD1 pregnant mice at different doses (range 0.1-30 μg/mouse), in single or multiple administrations. For biodistribution studies, fluorescently labeled PEG-SWCNTs were obtained by acylation of terminal PEG amino groups with near infrared emitting fluorochromes (PEG-SWCNT-750) and injected at the dosage of 10 μg/mouse, at either day 5.5 (when the placenta is still developing) or day 14.5 of gestation (when the maturation of the placenta is complete). RESULTS: We found no adverse effects both on embryos and dams up to the dose of 10 μg/mouse. At the dose of 30 μg/mouse, occasional teratogenic effects, associated with placental damage, were detected both when administered as a single bolus (1 out of 10 dams; 1 malformed embryo) or as multiple doses (2 out of 10 dams; 5 malformed embryos). The difference in the prevalence of dams with malformed embryos between the 30 μg exposed group and controls approached the statistical significance (p = 0.06). Hepatic damage in dams was seen only in the multiple exposure group (4 out of 10; p = 0.04 when compared with the single exposure group or controls). PEG-SWCNT-750 reached the conceptus when administered early in pregnancy. At later stages, PEG-SWCNT-750 were detected in the placenta and the yolk sac, but not in the embryo. CONCLUSIONS: PEG-SWCNTs may cause occasional teratogenic effects in mice beyond a threshold dose. Such effect might depend on their ability to reach the feto-placenta unit. Although not automatically transferable to humans, these data should be considered if exposing women during pregnancy. BioMed Central 2013-06-06 /pmc/articles/PMC3679973/ /pubmed/23742083 http://dx.doi.org/10.1186/1743-8977-10-21 Text en Copyright © 2013 Campagnolo et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Campagnolo, Luisa
Massimiani, Micol
Palmieri, Graziana
Bernardini, Roberta
Sacchetti, Cristiano
Bergamaschi, Antonio
Vecchione, Lucia
Magrini, Andrea
Bottini, Massimo
Pietroiusti, Antonio
Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice
title Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice
title_full Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice
title_fullStr Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice
title_full_unstemmed Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice
title_short Biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice
title_sort biodistribution and toxicity of pegylated single wall carbon nanotubes in pregnant mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679973/
https://www.ncbi.nlm.nih.gov/pubmed/23742083
http://dx.doi.org/10.1186/1743-8977-10-21
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