Translocation of poly(ethylene glycol-co-hexadecyl)cyanoacrylate nanoparticles into rat brain endothelial cells: role of apolipoproteins in receptor-mediated endocytosis.
Previous in vivo observations in rats have shown that poly(ethylene glycol) polyhexadecylcyanoacrylate (PEG-PHDCA) nanoparticles could translocate into the brain after intravenous injection, which polyhexadecylcyanoacrylate (PHDCA) nanoparticles did not. Through the detailed analysis of the plasma protein adsorption onto the surface of PEG-PHDCA nanoparticles, the present study aimed at clarifying the mechanism by which nanoparticles could penetrate into rat brain endothelial cells (RBEC). Two-dimensional polyacrylamide gel electrophoresis and Western blotting revealed that, after incubation with rat serum, apolipoprotein E (ApoE) adsorbed more onto PEG-PHDCA than on PHDCA nanoparticles. Adsorption of apolipoprotein B-100 (ApoB-100) onto PEG-PHDCA nanoparticles was demonstrated by capillary electrophoresis experiments. Moreover, only when ApoE or ApoB-100 were preadsorbed onto PEG-PHDCA nanoparticles, nanoparticles were found to be more efficient than control nanoparticles for penetrating into RBEC, suggesting the involvement of a low density lipoprotein receptor in this process. Thus, these data clearly demonstrate the involvement of apolipoproteins in the brain transport of PEG-PHDCA nanoparticles, which may open interesting prospects for brain drug delivery.
Kim
Hyun R
HR
Laboratory of Biopharmacy and Pharmaceutical Technology, UMR 8612, CNRS, University of Paris-Sud, F-92296 Châtenay-Malabry, France.
Andrieux
Karine
K
Gil
Sophie
S
Taverna
Myriam
M
Chacun
Héléne
H
Desmaële
Didier
D
Taran
Fréderic
F
Georgin
Dominique
D
Couvreur
Patrick
P
D000179:Acrylates / Q000737:chemistry; D000327:Adsorption; D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry*; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D003487:Cyanoacrylates / Q000737:chemistry*; D016503:Drug Delivery Systems; D019075:Electrophoresis, Capillary; D004705:Endocytosis; D042783:Endothelial Cells / Q000166:cytology*; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D016622:Silver Staining; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000179:Acrylates; D001053:Apolipoproteins; D003487:Cyanoacrylates; C121140:polyethyleneglycol polyhexadecylylcyanoacrylate copolymer; D011092:Polyethylene Glycols