title: Biocompatible Soft Nanoparticles with Multiple Morphologies Obtained from Nanoprecipitation of Amphiphilic Graft Copolymers in a Backbone-Selective Solvent.
abstract: Stealth nanocarriers are a promising technology for the treatment of diseases. However, the preparation and characterization of well-defined soft nanoparticulate systems remain challenging. Here we describe a platform of amphiphilic graft copolymers leading to nanoparticles with multiple morphologies and the role of the hydrophilic backbone in their interaction with a model protein. The amphiphilic graft copolymers platform was composed of hydrophilic backbone poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline) (P(MeOx-co-PentOx)), prepared via cationic ring-opening polymerization. Hydrophobic poly(d,l-lactide) (PLA) chains were grafted on the backbone via Huisgen 1,3-dipolar cycloaddition. The "click" copper-catalyzed cycloaddition reactions of azides with alkynes (CuAAC) were successfully carried out, and a series of amphiphilic copolymers were prepared containing a backbone with a number-average molecular weight of 14.2 × 103g mol-1and different hydrophobic PLA grafts with various molecular weights (2.8 × 103-12.4 × 103g mol-1). These original architectures of copolymers, when nanoprecipitated in water, the backbone-selective solvent, allowed us to obtain various structures of nanoparticles with a hydrodynamic diameter in the range of 65-99 nm. More interestingly, a plurality of morphologies going from unilamellar, multilamellar, and large compound vesicles to core-shell nanoparticles and depending on the PLA molecular weights were evidenced by combining cryo-transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS) studies. A first evaluation of their stealthiness by studying the stability and the interaction of these nano-objects with a model protein revealed the role played by the P(MeOx-co-PentOx) in these interactions, demonstrating the utility of this amphiphilic graft copolymers platform with well-defined architectures for the design of nanocarriers in drug delivery applications.
authors.affiliation: Université Paris Est , ICMPE (UMR7182), CNRS, UPEC, 94320 Thiais, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Le Fer
authors.affiliation: Université Paris Est , ICMPE (UMR7182), CNRS, UPEC, 94320 Thiais, France.|Laboratoire Léon Brillouin, UMR 12 CEA-CNRS, CEA Saclay , 91191 Gif-sur-Yvette Cedex, France.
authors.forename: Clémence
authors.identifier: 0000-0001-5072-1066
authors.initials: C
authors.lastname: Le Cœur
authors.affiliation: Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie (IMPMC), Sorbonne Universités , UPMC Paris 6, IRD, CNRS UMR7590, MNHN, 4 place Jussieu, 75252 Paris Cedex 05, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Guigner
authors.affiliation: Université Paris Est , ICMPE (UMR7182), CNRS, UPEC, 94320 Thiais, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Amiel
authors.affiliation: Université Paris Est , ICMPE (UMR7182), CNRS, UPEC, 94320 Thiais, France.|Université d'Evry Val d'Essonne , Rue du Père Jarlan, 91025 Evry Cedex, France.
authors.forename: Gisèle
authors.identifier: 0000-0003-1747-7895
authors.initials: G
authors.lastname: Volet