title: Low-density lipoprotein receptor-mediated endocytosis of PEGylated nanoparticles in rat brain endothelial cells.
abstract: Poly(methoxypolyethyleneglycol cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to diffuse through the blood-brain barrier after intravenous administration. However, the mechanism of transport of these nanoparticles into brain has not yet been clearly elucidated. The development of a model of rat brain endothelial cells (RBEC) in culture has allowed investigations into this mechanism. A study of the intracellular trafficking of nanoparticles by cell fractionation and confocal microscopy showed that nanoparticles are internalized by the endocytic pathway. Inhibition of the caveolae-mediated pathway by preincubation with filipin and nystatin did not modify the cellular uptake of the nanoparticles. In contrast, chlorpromazine and NaN(3) pretreatment, which interferes with clathrin and energy-dependent endocytosis, caused a significant decrease of nanoparticle internalization. Furthermore, cellular uptake experiments with nanoparticles preincubated with apolipoprotein E and blocking of low-density lipoprotein receptors (LDLR) clearly suggested that the LDLR-mediated pathway was involved in the endocytosis of PEGPHDCA nanoparticles by RBEC.
authors.affiliation: Laboratory of Biopharmacy and Pharmaceutical Technology, Faculty of Pharmacy, UMR 8612, IFR 141, CNRS, University of Paris-Sud 11, 5, rue J. B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: H Ryoung
authors.initials: HR
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Gil
authors.forename: K
authors.initials: K
authors.lastname: Andrieux
authors.forename: V
authors.initials: V
authors.lastname: Nicolas
authors.forename: M
authors.initials: M
authors.lastname: Appel
authors.forename: H
authors.initials: H
authors.lastname: Chacun
authors.forename: D
authors.initials: D
authors.lastname: Desmaële
authors.forename: F
authors.initials: F
authors.lastname: Taran
authors.forename: D
authors.initials: D
authors.lastname: Georgin
authors.forename: P
authors.initials: P
authors.lastname: Couvreur
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism; D003487:Cyanoacrylates / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000378:metabolism*; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D002966:Clathrin; D003487:Cyanoacrylates; D026901:Membrane Transport Proteins; D011973:Receptors, LDL; C504655:poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate); D011092:Polyethylene Glycols