title: Poly(trimethylene carbonate)/Poly(malic acid) Amphiphilic Diblock Copolymers as Biocompatible Nanoparticles.
abstract: Amphiphilic polycarbonate-poly(hydroxyalkanoate) diblock copolymers, namely, poly(trimethylene carbonate) (PTMC)-b-poly(β-malic acid) (PMLA), are reported for the first time. The synthetic strategy relies on commercially available catalysts and initiator. The controlled ring-opening polymerization (ROP) of trimethylene carbonate (TMC) catalyzed by the organic guanidine base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), associated with iPrOH as an initiator, provided iPrO-PTMC-OH, which served as a macroinitiator in the controlled ROP of benzyl β-malolactonate (MLABe) catalyzed by the neodymium triflate salt (Nd(OTf)3). The resulting hydrophobic iPrO-PTMC-b-PMLABe-OH copolymers were then hydrogenolyzed into the parent iPrO-PTMC-b-PMLA-OH copolymers. A range of well-defined copolymers, featuring different sizes of segments (Mn,NMR up to 9300 g mol(-1) ; ÐM =1.28-1.40), were thus isolated in gram quantities, as evidenced by NMR spectroscopy, size exclusion chromatography, thermogravimetric analysis, differential scanning calorimetry, and contact angle analyses. Subsequently, PTMC-b-PMLA copolymers with different hydrophilic weight fractions (11-75 %) self-assembled in phosphate-buffered saline upon nanoprecipitation into well-defined nano-objects with Dh =61-176 nm, a polydispersity index <0.25, and a negative surface charge, as characterized by dynamic light scattering and zeta-potential analyses. In addition, these nanoparticles demonstrated no significant effect on cell viability at low concentrations, and a very low cytotoxicity at high concentrations only for PTMC-b-PMLA copolymers exhibiting hydrophilic fractions over 47 %, thus illustrating the potential of these copolymers as promising nanoparticles.
authors.affiliation: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, 35042, Rennes Cedex, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Barouti
authors.affiliation: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, 35042, Rennes Cedex, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Khalil
authors.affiliation: Centre Régional de Mesures Physiques de l'Ouest, Université de Rennes 1, Campus de Beaulieu, 35042, Rennes Cedex, France.
authors.forename: Clement
authors.initials: C
authors.lastname: Orione
authors.affiliation: INSERM, UMR991, Liver, Metabolisms and Cancer, CHU Pontchaillou, 35033 Rennes Cedex -, Université de Rennes 1, 35043, Rennes Cedex, France.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Jarnouen
authors.affiliation: Ecole Nationale Supérieure de Chimie de Rennes, Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes 1, 11 Allée de Beaulieu CS 50837, 35708, Rennes Cedex, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cammas-Marion
authors.affiliation: INSERM, UMR991, Liver, Metabolisms and Cancer, CHU Pontchaillou, 35033 Rennes Cedex -, Université de Rennes 1, 35043, Rennes Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Loyer
authors.affiliation: Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS, Université de Rennes 1, Campus de Beaulieu, 263 Avenue du Général Leclerc, 35042, Rennes Cedex, France. sophie.guillaume@univ-rennes1.fr.
authors.forename: Sophie M
authors.identifier: http://orcid.org/0000-0003-2917-8657
authors.initials: SM
authors.lastname: Guillaume
mesh_terms: D053961:Azabicyclo Compounds / Q000737:chemistry*; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D004146:Dioxanes / Q000138:chemical synthesis / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008293:Malates / Q000138:chemical synthesis / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D053961:Azabicyclo Compounds; D001672:Biocompatible Materials; D004146:Dioxanes; D008293:Malates; D011108:Polymers; C121060:poly(malic acid); C526482:triazabicyclodecene; C059299:polytrimethylene carbonate
keywords: cytotoxicity; nanoparticles; polycabonate; polyhydroxyalkanoate; polymers; synthesis design