Translocation of poly(ethylene glycol-co-hexadecyl)cyanoacrylate nanoparticles into rat brain endothelial cells: role of apolipoproteins in receptor-mediated endocytosis.

Biomacromolecules

PubMedID: 17309294

Kim HR, Andrieux K, Gil S, Taverna M, Chacun H, Desmaële D, Taran F, Georgin D, Couvreur P. Translocation of poly(ethylene glycol-co-hexadecyl)cyanoacrylate nanoparticles into rat brain endothelial cells: role of apolipoproteins in receptor-mediated endocytosis. Biomacromolecules. 2007;8(3):793-9.
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.