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Reference : UMR5623-JEAMAR-005
Workplace : TOULOUSE
Date of publication : Monday, June 29, 2020
Scientific Responsible name : Jean-Daniel Marty
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 September 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Interest in the use of nanostructured materials in medicine and diagnostics has grown rapidly in recent years. The dimension of so-called nanomedicine results in new medical effects and requires novel, scientifically demanding chemistry. Thus, drug delivery systems with controllable size and shape in the nm range are needed to deliver bioactive agents and drugs for specific pathological and pharmacological purposes with improved bioavailability and pharmacokinetics. Among them organic-inorganic nanoparticles, which show great potential for imaging and diagnosis as well as for clinical therapeutics, have started to gain large interest. In order to develop new high sensitivity contrast agents while minimizing synthetic complexity, we plan to use hybrid polyion complexes obtained from complexation between metal ions and anionic block copolymers. Their formation is mainly driven by electrostatic interactions and entropy gain from the release of counter-ions. Moreover, coordination bonds confer an additional factor of stability towards salt addition or dilution, thus avoiding the need for prior encapsulation of metal ions in a specific complex structure. Relaxivity properties and high stability in biological medium obtained from preliminary experiments have shown the great potential of these systems. Hence the main objective of this project is to develop new versatile medical imaging nano-objects easily generated by the non-specific complexation of double hydrophilic block copolymers in presence of metal ions. Incorporation of different family of ions or polymers within these objects will enable to extent the proposed strategy to multimodal imaging (PET, MRI…) and will also enable to target specific probe.
Task 1: Design of original phosphonic acid-functional copolymers of controlled architecture and microstructure for the stabilization of bio-relevant inorganic interfaces.
- design of the hydrophilic block (nature of monomer, block length)
- design of the anionic block (nature of the phosphonate monomer, block length).
- strategies for the incorporation of a bio-probe at the end of the polymer chain.
Characterization techniques: NMR (1H, 13C NMR, 31P NMR), aqueous SEC, titration, DLS and many others.
Task 2: The second objective will be to associate the synthesized polymers with different ions of interest to design efficient contrast agents. We will fully explore the potential of such new HPICs formed with Gd3+ ions for MRI applications and to optimize their chemical, colloidal and in vivo stabilities. Preliminary experiments have demonstrated that cold Ga3+ ions also form HPICs when dispersed in a solution of copolymers. Therefore, the association of Ga3+ ions and copolymers could give rise to a new family of radiotracers for PET imaging. Moreover, combining Ga and Gd into a common HPIC nano-object may induce opportunities to combine PET and MRI imaging. This combination would allow the simultaneous measurement of perfusion and vascularization (via MRI) and metabolic processes (via PET). The nanooobjects will be studied through electronic microscopy, scattering experiments, UV-vis or fluorescence spectroscopy….
Task 3: The final task will be to develop functional contrast agents capable of being used in molecular imaging. For this purpose, polymers functionalized with a probe appropriate to the targeted application will be synthesized. The biological properties of these contrast agents will be evaluated in vitro and in vivo in collaboration with teams of biologists.
The thesis contract will take place in the IMRCP laboratory. The IMRCP laboratory is dedicated to the chemistry and physico-chemistry of soft matter and self-assembled systems. Based on synthetic compounds (such as surfactants or polymers), these systems offer a very wide range of technological and industrial applications. The thesis student will be assigned to the IDeAS team (about 30 people including 17 permanent staff) under the responsibility of Jean-Daniel Marty and to the P3R team (about 10 people including 5 permanent staff) under the responsibility of Mathias Destarac.
Funding within the framework of an ANR project
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