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Intership/PhD 2016-2017 - Contrast agents for stroke detection in mice using in vivo Magnetic Resonance Imaging

Université Paris Descartes: Isabelle Margaill (Pr)

Université Paris Descartes: Nathalie Mignet (CNRS)

Université Denis Diderot-MSC : Jean-François Berret (CNRS)

Project description

Stroke is a leading cause of death worldwide for which clinicians lack therapeutic strategies. Due to occlusion of a cerebral vessel, ischemic stroke represents 80% of all registered cases. Therapeutics should be personalized based on the mechanisms that occur at the stroke inception for a better chance of success. Non-invasive follow-up of biomarkers with molecular imaging may thus provide a solution for adjusting the treatment. The goal of our project is to develop innovative particles for Magnetic Resonance Imaging (MRI) to detect post-stroke vascular inflammation, in particular the adhesion molecule VCAM-1 implicated in leukocyte infiltration.

  1. The first step of the project will be the bottom-up fabrication of advanced MRI nanoprobes using iron oxide nanoparticles and advanced polymers, both being synthesized by us. The particles will be rendered specific by the covalent coupling of a peptide targeting VCAM-1 at their surface.
  2. The second step consists in optimizing the MRI probes for later in vitro and in vivo assays. The optimization process takes into account the stability of the probes in biological fluids, their relaxivity contrast properties and the degree of peptide conjugation. Biodistribution of imaging probes will be then studied in vivo in mice to check the detectability and stealthiness and to optimize the MRI procotol.
  3. Finally probes that will have passed through the above subsequent filters will be tested in an in vivo model of stroke to visualize the extent of the damaged tissues and vessels.

The outcome of our project will be the knowledge of innovative particles for post-stroke vascular inflammation. The originality of the project lies in three main points: the shape of the particles, the polymer coating and the adapted MRI sequences. The project will give new insights on the relation between particle shape and size and their efficiency as contrast agent, biodistribution and targeting adhesion properties. Beyond, the innovative particles developed in the project will open new avenues in the detection of other pathologies.

Description of the team that the student will join for the project

The intern will work with a joint team from the Université René Descartes (Paris 5) and Université Denis Diderot (Paris 7). The expertise of the two groups is complementary in the fields of nano/biomaterials, physical chemistry, Magnetic Resonance Imaging and stroke on mouse model. The originality of the present research is in the strong link with the Chemistry company Specific Polymers that provides us with up-to-date polymer coating.

At University Paris 7, the intern will join a group of 6 researchers, composed of 1 PhD (Fanny Mousseau), 2 postdocs (Leticia Vitorazi, one to be hired) and 3 permanent positions. The permanent positions are an ANR awarded “Chaire d’excellence” (Emek Seyrek), a biology engineer (Carine Vias) and a CNRS scientist (Jean-François Berret).

Recent References on this work

Q. L. Vuong, J.-F. Berret, J. Fresnais, Y. Gossuin and Ol. Sandre A Universal Scaling Law to Predict the Efficiency of Magnetic Nanoparticles as MRI T2-Contrast Agents, Advanced Health. Materials 1:502-512 (2012)

V. Torrisi, A. Graillot, L. Vitorazi, Q. Crouzet, G. Marletta, C. Loubat, and J.-F. Berret, Preventing corona effects: multi-phosphonic acid poly(ethylene glycol) copolymers for stable stealth iron oxide nanoparticles, Biomacromolecules, 2014, 15 (8), pp 3171–3179

M. Frechou, V. Beray-Berthat, J.S. Raynaud, S. Meriaux, F. Gombert, E. Lancelot, M. Plotkine, C. Marchand-Leroux, S. Ballet, P. Robert, G. Louin and I. Margaill, Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia. Contrast Media & Molecular Imaging 8, 157-164 (2013).


Biophysics, Materials and Soft Matter, Nanoparticles, Medical applications, biomaterials, biomimicry, Polymers, supramolecular polymers, polyelectrolytes, cytoskeleton, BERRET Jean-François, Proposition de stage ou de thèse, Ancienne proposition

Contact : Published on / Publié le 23 March 2017