title: Opsonisation of nanoparticles prepared from poly(β-hydroxybutyrate) and poly(trimethylene carbonate)-b-poly(malic acid) amphiphilic diblock copolymers: Impact on the in vitro cell uptake by primary human macrophages and HepaRG hepatoma cells.
abstract: The present work reports the investigation of the biocompatibility, opsonisation and cell uptake by human primary macrophages and HepaRG cells of nanoparticles (NPs) formulated from poly(β-malic acid)-b-poly(β-hydroxybutyrate) (PMLA-b-PHB) and poly(β-malic acid)-b-poly(trimethylene carbonate) (PMLA-b-PTMC) diblock copolymers, namely PMLA800-b-PHB7300, PMLA4500-b-PHB4400, PMLA2500-b-PTMC2800and PMLA4300-b-PTMC1400. NPs derived from PMLA-b-PHB and PMLA-b-PTMC do not trigger lactate dehydrogenase release and do not activate the secretion of pro-inflammatory cytokines demonstrating the excellent biocompatibility of these copolymers derived nano-objects. Using a protein adsorption assay, we demonstrate that the binding of plasma proteins is very low for PMLA-b-PHB-based nano-objects, and higher for those prepared from PMLA-b-PTMC copolymers. Moreover, a more efficient uptake by macrophages and HepaRG cells is observed for NPs formulated from PMLA-b-PHB copolymers compared to that of PMLA-b-PTMC-based NPs. Interestingly, the uptake in HepaRG cells of NPs formulated from PMLA800-b-PHB7300is much higher than that of NPs based on PMLA4500-b-PHB4400. In addition, the cell internalization of PMLA800-b-PHB7300based-NPs, probably through endocytosis, is strongly increased by serum pre-coating in HepaRG cells but not in macrophages. Together, these data strongly suggest that the binding of a specific subset of plasmatic proteins onto the PMLA800-b-PHB7300-based NPs favors the HepaRG cell uptake while reducing that of macrophages.
authors.affiliation: INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Vene
authors.affiliation: Institut des Sciences Chimiques de Rennes; UMR 6226 CNRS; Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, F-35042 Rennes Cedex, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Barouti
authors.affiliation: INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jarnouen
authors.affiliation: INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gicquel
authors.affiliation: INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Rauch
authors.affiliation: INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ribault
authors.affiliation: Institut des Sciences Chimiques de Rennes; UMR 6226 CNRS; Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, F-35042 Rennes Cedex, France.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Guillaume
authors.affiliation: Ecole Nationale Supérieure de Chimie de Rennes, Institute des Sciences Chimiques de Rennes, Université de Rennes 1, 11 allée de Beaulieu, CS 50837, 35708 Rennes Cedex 7, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cammas-Marion
authors.affiliation: INSERM UMR S-991, Foie, Métabolismes et Cancer; Université de Rennes 1; CHU Pontchaillou Rennes, 35033 Rennes, France. Electronic address: pascal.loyer@univ-rennes1.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Loyer
mesh_terms: D001692:Biological Transport; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004146:Dioxanes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006885:Hydroxybutyrates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008113:Liver Neoplasms; D008264:Macrophages / Q000378:metabolism; D008293:Malates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000091402:Prohibitins; D000094122:Polyhydroxybutyrates
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D004146:Dioxanes; D006885:Hydroxybutyrates; D007770:L-Lactate Dehydrogenase; D008293:Malates; D011091:Polyesters; D011108:Polymers; D000091402:Prohibitins; C000717328:PHB protein, human; C121060:poly(malic acid); C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates; C059299:polytrimethylene carbonate
keywords: HepaRG cells; Macrophages; Nanoparticle; Poly(hydroxy alkanoate); Poly(malic acid); Poly(trimethylene carbonate)