title: Protein adsorption and complement activation for di-block copolymer nanoparticles.
abstract: Four types of nanoparticles with core-diffuse shell structures have been synthesized through self-assembly of PICBA-Dextran block copolymers. These nanoparticles are designed to carry pharmaceutically active molecules into the human body through injection into the blood stream. In this work, we have determined how the characteristics of the diffuse shell influence the adsorption of three types of proteins: Bovine Serum Albumin (BSA), fibrinogen, and a protein from the complement system that triggers recognition and elimination by macrophages. We have determined the structural characteristics of the diffuse shells using Nuclear Magnetic Resonance (NMR), Small Angle Neutron Scattering (SANS) and Quasi-Elastic Light Scattering (QELS). We have measured the adsorption of Bovine Serum Albumin (BSA) through Immunodiffusion methods, and found that it adsorbed in substantial amounts even when the distance between dextran chains at the core-diffuse shell interface is quite short. We have observed the aggregation of the nanoparticles induced by fibrinogen, and found that it was prevented when the density of dextran chains protruding from the core surface was sufficiently high. Finally we have measured the activation of the complement system by the nanoparticles, and found that it was also limited by the surface density of dextran chains that protrude from the core and by their mesh size within the diffuse shell.
authors.affiliation: Univ Paris Sud, Physico-chimie Pharmacotechnie Biopharmacie, UMR CNRS 8612, F-92296 Chatenay-Malabry, France. Christine.vauthier@u-pusd.fr
authors.forename: Christine
authors.initials: C
authors.lastname: Vauthier
authors.forename: Bjorn
authors.initials: B
authors.lastname: Persson
authors.forename: Peter
authors.initials: P
authors.lastname: Lindner
authors.forename: Bernard
authors.initials: B
authors.lastname: Cabane
mesh_terms: D000327:Adsorption; D000818:Animals; D002417:Cattle; D003167:Complement Activation / Q000187:drug effects*; D005340:Fibrinogen / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D011108:Polymers; D012710:Serum Albumin, Bovine; D005340:Fibrinogen