Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation

Abstract Multimodal polymeric nanoparticles have many exciting diagnostic and therapeutic applications, yet their uptake and passage by the placenta, and applications in the treatment of pregnancy complications have not been thoroughly investigated. In this work, the maternal-fetal-placental biodist...

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Autores principales: Diwei Ho, Joan W. Leong, Rachael C. Crew, Marck Norret, Michael J. House, Peter J. Mark, Brendan J. Waddell, K. Swaminathan Iyer, Jeffrey A. Keelan
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/d71b1a33261042c09828b0d99a3ce0ad
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spelling oai:doaj.org-article:d71b1a33261042c09828b0d99a3ce0ad2021-12-02T12:32:13ZMaternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation10.1038/s41598-017-03128-72045-2322https://doaj.org/article/d71b1a33261042c09828b0d99a3ce0ad2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03128-7https://doaj.org/toc/2045-2322Abstract Multimodal polymeric nanoparticles have many exciting diagnostic and therapeutic applications, yet their uptake and passage by the placenta, and applications in the treatment of pregnancy complications have not been thoroughly investigated. In this work, the maternal-fetal-placental biodistribution of anionic and cationic multimodal poly(glycidyl methacrylate) (PGMA) nanoparticles in pregnant rats at mid (ED10) and late (ED20) gestation was examined. Fluorescently-labelled and superparamagnetic PGMA nanoparticles functionalized with/without poly(ethyleneimine) (PEI) were administered to pregnant rats at a clinically-relevant dose and biodistribution and tissue uptake assessed. Quantitative measurement of fluorescence intensity or magnetic resonance relaxometry in tissue homogenates lacked the sensitivity to quantify tissue uptake. Confocal microscopy, however, identified uptake by maternal organs and the decidua (ectoplacental cone) and trophoblast giant cells of conceptuses at ED10. At ED20, preferential accumulation of cationic vs. anionic nanoparticles was observed in the placenta, with PGMA-PEI nanoparticles localised mainly within the chorionic plate. These findings highlight the significant impact of surface charge and gestational age in the biodistribution of nanoparticles in pregnancy, and demonstrate the importance of using highly sensitive measurement techniques to evaluate nanomaterial biodistribution and maternal-fetal exposure.Diwei HoJoan W. LeongRachael C. CrewMarck NorretMichael J. HousePeter J. MarkBrendan J. WaddellK. Swaminathan IyerJeffrey A. KeelanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Diwei Ho
Joan W. Leong
Rachael C. Crew
Marck Norret
Michael J. House
Peter J. Mark
Brendan J. Waddell
K. Swaminathan Iyer
Jeffrey A. Keelan
Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation
description Abstract Multimodal polymeric nanoparticles have many exciting diagnostic and therapeutic applications, yet their uptake and passage by the placenta, and applications in the treatment of pregnancy complications have not been thoroughly investigated. In this work, the maternal-fetal-placental biodistribution of anionic and cationic multimodal poly(glycidyl methacrylate) (PGMA) nanoparticles in pregnant rats at mid (ED10) and late (ED20) gestation was examined. Fluorescently-labelled and superparamagnetic PGMA nanoparticles functionalized with/without poly(ethyleneimine) (PEI) were administered to pregnant rats at a clinically-relevant dose and biodistribution and tissue uptake assessed. Quantitative measurement of fluorescence intensity or magnetic resonance relaxometry in tissue homogenates lacked the sensitivity to quantify tissue uptake. Confocal microscopy, however, identified uptake by maternal organs and the decidua (ectoplacental cone) and trophoblast giant cells of conceptuses at ED10. At ED20, preferential accumulation of cationic vs. anionic nanoparticles was observed in the placenta, with PGMA-PEI nanoparticles localised mainly within the chorionic plate. These findings highlight the significant impact of surface charge and gestational age in the biodistribution of nanoparticles in pregnancy, and demonstrate the importance of using highly sensitive measurement techniques to evaluate nanomaterial biodistribution and maternal-fetal exposure.
format article
author Diwei Ho
Joan W. Leong
Rachael C. Crew
Marck Norret
Michael J. House
Peter J. Mark
Brendan J. Waddell
K. Swaminathan Iyer
Jeffrey A. Keelan
author_facet Diwei Ho
Joan W. Leong
Rachael C. Crew
Marck Norret
Michael J. House
Peter J. Mark
Brendan J. Waddell
K. Swaminathan Iyer
Jeffrey A. Keelan
author_sort Diwei Ho
title Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation
title_short Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation
title_full Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation
title_fullStr Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation
title_full_unstemmed Maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation
title_sort maternal-placental-fetal biodistribution of multimodal polymeric nanoparticles in a pregnant rat model in mid and late gestation
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/d71b1a33261042c09828b0d99a3ce0ad
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