Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier

Nanoparticle (NP)-assisted procedures including laser tissue soldering (LTS) offer advantages compared to conventional microsuturing, especially in the brain. In this study, effects of polymer-coated silica NPs used in LTS were investigated in human brain endothelial cells (ECs) and blood-brain barr...

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Main Authors: Aniela Bittner, Fabien Gosselet, Emmanuel Sevin, Lucie Dehouck, Angélique D. Ducray, Véronique Gaschen, Michael H. Stoffel, Hansang Cho, Meike Mevissen
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/4/1657
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author Aniela Bittner
Fabien Gosselet
Emmanuel Sevin
Lucie Dehouck
Angélique D. Ducray
Véronique Gaschen
Michael H. Stoffel
Hansang Cho
Meike Mevissen
author_facet Aniela Bittner
Fabien Gosselet
Emmanuel Sevin
Lucie Dehouck
Angélique D. Ducray
Véronique Gaschen
Michael H. Stoffel
Hansang Cho
Meike Mevissen
author_sort Aniela Bittner
collection DOAJ
description Nanoparticle (NP)-assisted procedures including laser tissue soldering (LTS) offer advantages compared to conventional microsuturing, especially in the brain. In this study, effects of polymer-coated silica NPs used in LTS were investigated in human brain endothelial cells (ECs) and blood-brain barrier models. In the co-culture setting with ECs and pericytes, only the cell type directly exposed to NPs displayed a time-dependent internalization. No transfer of NPs between the two cell types was observed. Cell viability was decreased relatively to NP exposure duration and concentration. Protein expression of the nuclear factor ĸ-light-chain-enhancer of activated B cells and various endothelial adhesion molecules indicated no initiation of inflammation or activation of ECs after NP exposure. Differentiation of CD34+ ECs into brain-like ECs co-cultured with pericytes, blood-brain barrier (BBB) characteristics were obtained. The established endothelial layer reduced the passage of integrity tracer molecules. NP exposure did not result in alterations of junctional proteins, BBB formation or its integrity. In a 3-dimensional setup with an endothelial tube formation and tight junctions, barrier formation was not disrupted by the NPs and NPs do not seem to cross the blood-brain barrier. Our findings suggest that these polymer-coated silica NPs do not damage the BBB.
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spelling doaj.art-8b2e1413ffe347b1b2dc89281fa3114b2023-12-03T12:41:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224165710.3390/ijms22041657Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain BarrierAniela Bittner0Fabien Gosselet1Emmanuel Sevin2Lucie Dehouck3Angélique D. Ducray4Véronique Gaschen5Michael H. Stoffel6Hansang Cho7Meike Mevissen8Division of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, 3012 Bern, SwitzerlandBlood-Brain-Barrier Laboratory, University of Artois, UR265, Faculté Jean Perrin, Rue Jean Souvraz–SP 18, 62307 Lens, FranceBlood-Brain-Barrier Laboratory, University of Artois, UR265, Faculté Jean Perrin, Rue Jean Souvraz–SP 18, 62307 Lens, FranceBlood-Brain-Barrier Laboratory, University of Artois, UR265, Faculté Jean Perrin, Rue Jean Souvraz–SP 18, 62307 Lens, FranceDivision of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, 3012 Bern, SwitzerlandDivision of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Länggassstrasse 120, 3012 Bern, SwitzerlandDivision of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, Länggassstrasse 120, 3012 Bern, SwitzerlandInstitute of Quantum Biophysics, Department of Biophysics, Department of Intelligent Precision Healthcare Concergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, #868715 N-Center Suwon-si, Gyeonggi-do 16419, KoreaDivision of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, 3012 Bern, SwitzerlandNanoparticle (NP)-assisted procedures including laser tissue soldering (LTS) offer advantages compared to conventional microsuturing, especially in the brain. In this study, effects of polymer-coated silica NPs used in LTS were investigated in human brain endothelial cells (ECs) and blood-brain barrier models. In the co-culture setting with ECs and pericytes, only the cell type directly exposed to NPs displayed a time-dependent internalization. No transfer of NPs between the two cell types was observed. Cell viability was decreased relatively to NP exposure duration and concentration. Protein expression of the nuclear factor ĸ-light-chain-enhancer of activated B cells and various endothelial adhesion molecules indicated no initiation of inflammation or activation of ECs after NP exposure. Differentiation of CD34+ ECs into brain-like ECs co-cultured with pericytes, blood-brain barrier (BBB) characteristics were obtained. The established endothelial layer reduced the passage of integrity tracer molecules. NP exposure did not result in alterations of junctional proteins, BBB formation or its integrity. In a 3-dimensional setup with an endothelial tube formation and tight junctions, barrier formation was not disrupted by the NPs and NPs do not seem to cross the blood-brain barrier. Our findings suggest that these polymer-coated silica NPs do not damage the BBB.https://www.mdpi.com/1422-0067/22/4/1657co-culture3D modelpermeabilitytransendothelial electrical resistance
spellingShingle Aniela Bittner
Fabien Gosselet
Emmanuel Sevin
Lucie Dehouck
Angélique D. Ducray
Véronique Gaschen
Michael H. Stoffel
Hansang Cho
Meike Mevissen
Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier
International Journal of Molecular Sciences
co-culture
3D model
permeability
transendothelial electrical resistance
title Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier
title_full Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier
title_fullStr Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier
title_full_unstemmed Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier
title_short Time-Dependent Internalization of Polymer-Coated Silica Nanoparticles in Brain Endothelial Cells and Morphological and Functional Effects on the Blood-Brain Barrier
title_sort time dependent internalization of polymer coated silica nanoparticles in brain endothelial cells and morphological and functional effects on the blood brain barrier
topic co-culture
3D model
permeability
transendothelial electrical resistance
url https://www.mdpi.com/1422-0067/22/4/1657
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