title: Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Cell Biology and Applied Virology, Fraunhofer Institute for Biomedical Engineering, St. Ingbert, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Anja
authors.initials: A
authors.lastname: Zensi
authors.forename: Sascha L
authors.initials: SL
authors.lastname: Wien
authors.forename: Sabrina E
authors.initials: SE
authors.lastname: Tschickardt
authors.forename: Wladislaw
authors.initials: W
authors.lastname: Maier
authors.forename: Tikva
authors.initials: T
authors.lastname: Vogel
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: Claus U
authors.initials: CU
authors.lastname: Pietrzik
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D001927:Brain Diseases / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D012709:Serum Albumin