Translocation of Poly(ethylene glycol-co-hexadecyl)cyanoacrylate Nanoparticles into Rat Brain Endothelial Cells:  Role of Apolipoproteins in Receptor-Mediated Endocytosis

• Published in: Biomacromolecules Vol. 8; no. 3; pp. 793 - 799
• Main Authors: Kim, Hyun R, Andrieux, Karine, Gil, Sophie, Taverna, Myriam, Chacun, Héléne, Desmaële, Didier, Taran, Fréderic, Georgin, Dominique, Couvreur, Patrick
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-03-2007
• Subjects: Acrylates - chemistry; Adsorption; Animals; Apolipoproteins - chemistry; Applied sciences; Biological and medical sciences; Biological Transport; Brain - metabolism; Cyanoacrylates - chemistry; Drug Delivery Systems; Electrophoresis, Capillary; Endocytosis; Endothelial Cells - cytology; Exact sciences and technology; Forms of application and semi-finished materials; General pharmacology; Medical sciences; Miscellaneous; Nanoparticles - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; Polymer industry, paints, wood; Rats; Silver Staining; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Technology of polymers; Translocation; Endothelial cell; Rat; Liquid solid adsorption; Nanoparticle; Control release polymer; Alkyl acrylate(cyano) copolymer; Rodentia; Drug carrier; Apolipoprotein; Ethylene oxide copolymer; Experimental study; Blood brain barrier; Mechanism; Vertebrata; Endocytosis; Mammalia; Animal
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm060711a

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.