PhD candidate in physico-chemistry of anisotropic polymer nanoparticles (M/F)

Updated: 29 days ago
Location: Tremblay en France, LE DE FRANCE
Deadline: 10 Sep 2019

The Laboratory of Chemistry of Organic Polymers (LCPO) is a joint research unit affiliated to the CNRS, the University of Bordeaux and the Institut Polytechnique de Bordeaux ( ). The LCPO is organized into 4 research teams with a total strength of nearly 150 people, including about 50 permanent staff.
With over 30 years of expertise in polymer chemistry, researches at LCPO aim at:
- developing innovative methodologies for precision synthesis of polymers, using in particular biomimetic and/or green chemistry pathways
- designing functional polymer materials by macromolecular engineering and self-assembly, in the fields of renewable materials, health and energy
- establishing strong links with the socio-economy world.
The work of the recruited agent will be carried out in team 3 of the LCPO and in collaboration with the partners of the MAVERICK project.
Team 3 entitled "Self-assembly of Polymers and Life Sciences" is headed by Sébastien Lecommandoux. The team explores the design biomimetic and biofuntional nano and microparticles, especially polymersomes, with the following main focus:
- synthesis and self-assembly of block copolymers based on polypeptides, polysaccharides and proteins
- formulation of functional nanoparticles, including polymersomes, for the targeted delivery and controlled release of active ingredients (therapy and theranostic)
- design of artificial cells (protocells) as membrane models and biological factory.

The MAVERICK project (MAgnetic VEsicle Rotation-Induced Cell-Killing) funded by French research agency aims at developing anisotropically shaped nano-vectors, in order to specifically kill cancer cells by applying magnetic torques on cellular membranes. The studied systems will be magnetic polymersomes, a type of nanovectors developed in 2005 by our group at LCPO. They are a spectacular example of versatile nanovectors capable of releasing active substances at a tumor site under the action of a high frequency (HF) magnetic field that provokes local (i.e. nanoscale) heating of the membrane, enhancing its permeability. In a static magnetic field, these nano-objects undergo substantial elongation. If one fixes that shape by chemical crosslinking under magnetic field, these anisometric entities will give access to new delivery modes, such as the application of a magnetic torque on the cellular membranes (outer plasma membrane and intracellular organelle membranes) by applying a low frequency (LF) magnetic field. The MAVERICK project aims at studying the ellipsoid-like or more complex deformations of magnetic polymersomes (Work-Package 1), the biocompatibility and internalization pathways as a function of polymersome morphologies (Work-Package 2), and the magneto-induced toxicity on cells induced by LF or HF magnetic fields (Worl-Package 3). WP2 and WP3 will be accomplished in collaboration with a group of biologists at the INSA Toulouse and with the Bordeaux Imaging Center for electron microscopy experiment on biological cells. At first, the PhD candidate will work in WP1 on the synthesis of polymers and magnetic iron oxide nanoparticles for the preparation of several types of magnetic polymersomes (MagPol), starting from amphiphilic di-block copolymers whose hydrophilic block is poly(oxyethylene) (POE) and hydrophobic block either poly(butadiene) (PBut) or poly(trimethylene carbonate) (PTMC), in which magnetic iron oxide nanoparticles (IONPs) will be embedded through a self-assembly process (nanoprecipitation). Deformation of these soft magnetic shells under a static magnetic field will be studied theoretically by numerical simulation (in collaboration with a Russian theoretician team) and by several experimental methods: electron microscopy, dynamic depolarized scattering (DDLS) and small angle neutron scattering (SANS). The novelty compared to previous studies will consist in a "quench" of the expected elongated shapes of MagPol under field through chemical crosslinking of the hydrophobic blocks of copolymers. Different crosslinking reactions will be tried out, first by radical initiation by an oxidizing agent for PBut, and also by photo-crosslinking induced par UV irradiation UV for PBut and PTMC (with the aid of copolymerization with a monomer bearing pendant unsaturated groups), or even under gamma ray radiation (in collaboration with the VINCA institute of nuclear research in Belgrade, Serbbia). One last type of polymersomes will comprise semi-crystalline polymers blocks (PTMC or poly(caprolactone)) to introduce also thermosensitivity. The candidate is expected to have good skills in chemistry and physico-chemistry of polymers, with an interest for the interface with biology (nanomedicine).

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