TY - JOUR A1 - Wagner, Sylvia A1 - Zensi, Anja A1 - Wien, Sascha L. A1 - Tschickardt, Sabrina E. A1 - Maier, Wladislaw A1 - Vogel, Tikva A1 - Worek, Franz A1 - Pietrzik, Claus Ulrich A1 - Kreuter, Jörg A1 - Briesen, Hagen von T1 - Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model T2 - PLoS One N2 - 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. Y1 - 2012 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24574 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-245742 SN - 1932-6203 VL - 7 IS - 3: e32568 SP - 1 EP - 7 PB - PLoS CY - Lawrence, Kan. ER -