title: Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush.
abstract: The aim of this work was to examine the in vitro interactions of core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles (NP) with blood proteins. The particles were prepared by initiating the emulsion polymerization of isobutylcyanoacrylate (IBCA) in the presence of dextran 71 or 15 kDa, heparin, a blend of dextran 71 and heparin, or dextran sulphate in aqueous medium at pH 1. The mechanisms of polymerisation were redox radical (Rad) or anionic (An), resulting in differences in the spatial arrangement of the polysaccharide chains at the NP surface, i.e. "loops" and "trains" by anionic polymerization, "brush" by radical polymerization. Surface composition of NPs was determined by X-ray photo-electron spectroscopy (XPS) and surface charge by zeta potential measurements. In the presence of citrated blood plasma, efficacy of the steric repulsive effect of the NP dextran shell towards protein adsorption decreased in the order: Dex71-Rad > Dex15-Rad > Dex71-AnDex15-An. Dextran-coated NPs adsorbed ApoA-I and fibrinogen from plasma. Concerning activation of complement in serum, the effect was sharp: Dex71-Rad was a very low activator whereas Dex15-An, Dex15-Rad and Dex71-An were strong activators. In citrated plasma, the steric repulsive effects of Hep-Rad and Dex-Hep-Rad NPs were similar to Dex71-An, and Dex-Sulph-Rad NPs adsorbed twice more proteins than Hep-Rad. Hep-Rad, Dex-Hep-Rad and Dex-Sulph-Rad NPs adsorbed IgG and fibrinogen. Complement was not activated in serum in the presence of Hep-Rad and Dex-Hep-Rad and a slight adsorption of C3 was noted. C3 was completely adsorbed on Dex-Sulph-Rad. The exquisite sensitivity of blood proteins to differences in the nature and outermost structure of the polysaccharides-coated NPs is highlighted by the present results.
authors.affiliation: Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Université Paris Sud-XI, 5 rue JB Clement, 92296 Châtenay-Malabry Cedex, France. denis.labarre@cep.u-psud.fr
authors.forename: Denis
authors.initials: D
authors.lastname: Labarre
authors.forename: Christine
authors.initials: C
authors.lastname: Vauthier
authors.forename: Cédric
authors.initials: C
authors.lastname: Chauvierre
authors.forename: Boris
authors.initials: B
authors.lastname: Petri
authors.forename: Rainer
authors.initials: R
authors.lastname: Müller
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Chehimi
mesh_terms: D000327:Adsorption; D001798:Blood Proteins / Q000032:analysis / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000032:analysis / Q000737:chemistry*; D003487:Cyanoacrylates / Q000032:analysis / Q000737:chemistry*; D004659:Enbucrilate; D008422:Materials Testing; D043942:Nanotubes / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000032:analysis / Q000737:chemistry*; D011134:Polysaccharides / Q000032:analysis / Q000737:chemistry*; D011485:Protein Binding; D013499:Surface Properties
chemical_list: D001798:Blood Proteins; D020099:Coated Materials, Biocompatible; D003487:Cyanoacrylates; D011108:Polymers; D011134:Polysaccharides; D004659:Enbucrilate