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 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.

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Metadaten
Author:Sylvia Wagner, Anja Zensi, Sascha L. Wien, Sabrina E. Tschickardt, Wladislaw Maier, Tikva Vogel, Franz Worek, Claus Ulrich Pietrzik, Jörg KreuterGND, Hagen von BriesenORCiD
URN:urn:nbn:de:hebis:30:3-245742
DOI:https://doi.org/doi:10.1371/journal.pone.0032568
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/22396775
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Year of first Publication:2012
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/03/27
Volume:7
Issue:3: e32568
Page Number:7
First Page:1
Last Page:7
HeBIS-PPN:29303575X
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0