Distribution of SiO2 nanoparticles in 3D liver microtissues

Jana Fleddermann,1 Julia Susewind,2 Henrike Peuschel,1 Marcus Koch,1 Isabella Tavernaro,1 Annette Kraegeloh1 1INM – Leibniz Institute for New Materials, Saarbrücken, Germany; 2Pharmacelsus GmbH, Saarbrücken, Germany Introduction: Nanoparticles (NPs) are used in numerous...

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Autores principales: Fleddermann J, Susewind J, Peuschel H, Koch M, Tavernaro I, Kraegeloh A
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:04273b4c5e9f4b4397df4a903d6c66122021-12-02T07:14:39ZDistribution of SiO2 nanoparticles in 3D liver microtissues1178-2013https://doaj.org/article/04273b4c5e9f4b4397df4a903d6c66122019-02-01T00:00:00Zhttps://www.dovepress.com/distribution-of-sio2-nanoparticles-in-3d-liver-microtissues-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jana Fleddermann,1 Julia Susewind,2 Henrike Peuschel,1 Marcus Koch,1 Isabella Tavernaro,1 Annette Kraegeloh1 1INM – Leibniz Institute for New Materials, Saarbrücken, Germany; 2Pharmacelsus GmbH, Saarbrücken, Germany Introduction: Nanoparticles (NPs) are used in numerous products in technical fields and biomedicine; their potential adverse effects have to be considered in order to achieve safe applications. Besides their distribution in tissues, organs, and cellular localization, their impact and penetration during the process of tissue formation occurring in vivo during liver regeneration are critical steps for establishment of safe nanomaterials.Materials and methods: In this study, 3D cell culture of human hepatocarcinoma cells (HepG2) was used to generate cellular spheroids, serving as in vitro liver microtissues. In order to determine their differential distribution and penetration depth in HepG2 spheroids, SiO2 NPs were applied either during or after spheroid formation. The NP penetration was comprehensively studied using confocal laser scanning microscopy and scanning electron microscopy.Results: Spheroids were exposed to 100 µg mL-1 SiO2 NPs either at the beginning of spheroid formation, or during or after formation of spheroids. Microscopy analyses revealed that NP penetration into the spheroid is limited. During and after spheroid formation, SiO2 NPs penetrated about 20 µm into the spheroids, corresponding to about three cell layers. In contrast, because of the addition of SiO2 NPs simultaneously to cell seeding, NP agglomerates were located also in the spheroid center. Application of SiO2 NPs during the process of spheroid formation had no impact on final spheroid size.Conclusion: Understanding the distribution of NPs in tissues is essential for biomedical applications. The obtained results indicate that NPs show only limited penetration into already formed tissue, which is probably caused by the alteration of the tissue structure and cell packing density during the process of spheroid formation. Keywords: silica nanoparticles, human hepatocarcinoma cells, spheroids, penetration  Fleddermann JSusewind JPeuschel HKoch MTavernaro IKraegeloh ADove Medical PressarticleSilica nanoparticlesHuman hepatocarcinoma cellsSpheroidsPenetrationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 1411-1431 (2019)
institution DOAJ
collection DOAJ
language EN
topic Silica nanoparticles
Human hepatocarcinoma cells
Spheroids
Penetration
Medicine (General)
R5-920
spellingShingle Silica nanoparticles
Human hepatocarcinoma cells
Spheroids
Penetration
Medicine (General)
R5-920
Fleddermann J
Susewind J
Peuschel H
Koch M
Tavernaro I
Kraegeloh A
Distribution of SiO2 nanoparticles in 3D liver microtissues
description Jana Fleddermann,1 Julia Susewind,2 Henrike Peuschel,1 Marcus Koch,1 Isabella Tavernaro,1 Annette Kraegeloh1 1INM – Leibniz Institute for New Materials, Saarbrücken, Germany; 2Pharmacelsus GmbH, Saarbrücken, Germany Introduction: Nanoparticles (NPs) are used in numerous products in technical fields and biomedicine; their potential adverse effects have to be considered in order to achieve safe applications. Besides their distribution in tissues, organs, and cellular localization, their impact and penetration during the process of tissue formation occurring in vivo during liver regeneration are critical steps for establishment of safe nanomaterials.Materials and methods: In this study, 3D cell culture of human hepatocarcinoma cells (HepG2) was used to generate cellular spheroids, serving as in vitro liver microtissues. In order to determine their differential distribution and penetration depth in HepG2 spheroids, SiO2 NPs were applied either during or after spheroid formation. The NP penetration was comprehensively studied using confocal laser scanning microscopy and scanning electron microscopy.Results: Spheroids were exposed to 100 µg mL-1 SiO2 NPs either at the beginning of spheroid formation, or during or after formation of spheroids. Microscopy analyses revealed that NP penetration into the spheroid is limited. During and after spheroid formation, SiO2 NPs penetrated about 20 µm into the spheroids, corresponding to about three cell layers. In contrast, because of the addition of SiO2 NPs simultaneously to cell seeding, NP agglomerates were located also in the spheroid center. Application of SiO2 NPs during the process of spheroid formation had no impact on final spheroid size.Conclusion: Understanding the distribution of NPs in tissues is essential for biomedical applications. The obtained results indicate that NPs show only limited penetration into already formed tissue, which is probably caused by the alteration of the tissue structure and cell packing density during the process of spheroid formation. Keywords: silica nanoparticles, human hepatocarcinoma cells, spheroids, penetration  
format article
author Fleddermann J
Susewind J
Peuschel H
Koch M
Tavernaro I
Kraegeloh A
author_facet Fleddermann J
Susewind J
Peuschel H
Koch M
Tavernaro I
Kraegeloh A
author_sort Fleddermann J
title Distribution of SiO2 nanoparticles in 3D liver microtissues
title_short Distribution of SiO2 nanoparticles in 3D liver microtissues
title_full Distribution of SiO2 nanoparticles in 3D liver microtissues
title_fullStr Distribution of SiO2 nanoparticles in 3D liver microtissues
title_full_unstemmed Distribution of SiO2 nanoparticles in 3D liver microtissues
title_sort distribution of sio2 nanoparticles in 3d liver microtissues
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/04273b4c5e9f4b4397df4a903d6c6612
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