Uptake Mechanism of ApoE-modified Nanoparticles on Brain Capillary Endothelial Cells As a Blood-brain Barrier Model

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Mar 8

PMID 22396775

Citations 80

Authors

Sylvia Wagner

Anja Zensi

Sascha L Wien

Sabrina E Tschickardt

Wladislaw Maier

Tikva Vogel

Franz Worek

Claus U Pietrzik

Jorg Kreuter

Hagen von Briesen

Affiliations

Soon will be listed here.

Abstract

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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