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Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model
BACKGROUND: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotei...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291552/ https://www.ncbi.nlm.nih.gov/pubmed/22396775 http://dx.doi.org/10.1371/journal.pone.0032568 |
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author | Wagner, Sylvia Zensi, Anja Wien, Sascha L. Tschickardt, Sabrina E. Maier, Wladislaw Vogel, Tikva Worek, Franz Pietrzik, Claus U. Kreuter, Jörg von Briesen, Hagen |
author_facet | Wagner, Sylvia Zensi, Anja Wien, Sascha L. Tschickardt, Sabrina E. Maier, Wladislaw Vogel, Tikva Worek, Franz Pietrzik, Claus U. Kreuter, Jörg von Briesen, Hagen |
author_sort | Wagner, Sylvia |
collection | PubMed |
description | BACKGROUND: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. CONCLUSIONS/SIGNIFICANCE: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier. |
format | Online Article Text |
id | pubmed-3291552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32915522012-03-06 Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model Wagner, Sylvia Zensi, Anja Wien, Sascha L. Tschickardt, Sabrina E. Maier, Wladislaw Vogel, Tikva Worek, Franz Pietrzik, Claus U. Kreuter, Jörg von Briesen, Hagen PLoS One Research Article BACKGROUND: The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. CONCLUSIONS/SIGNIFICANCE: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier. Public Library of Science 2012-03-01 /pmc/articles/PMC3291552/ /pubmed/22396775 http://dx.doi.org/10.1371/journal.pone.0032568 Text en Wagner et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wagner, Sylvia Zensi, Anja Wien, Sascha L. Tschickardt, Sabrina E. Maier, Wladislaw Vogel, Tikva Worek, Franz Pietrzik, Claus U. Kreuter, Jörg von Briesen, Hagen Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model |
title | Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model |
title_full | Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model |
title_fullStr | Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model |
title_full_unstemmed | Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model |
title_short | Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model |
title_sort | uptake mechanism of apoe-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291552/ https://www.ncbi.nlm.nih.gov/pubmed/22396775 http://dx.doi.org/10.1371/journal.pone.0032568 |
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