Thèse Nanomédicaments Micellaires pour la Radiothérapie Interne Vectorisée H/F - 75

Établissement : Université Paris-Saclay GS Chimie
École doctorale : Sciences Chimiques : Molécules, Matériaux, Instrumentation et Biosystèmes
Laboratoire de recherche : Médicaments et Technologies pour la Santé
Direction de la thèse : Eric DORIS ORCID 000000031318602X
Début de la thèse : 2026-10-01
Date limite de candidature : 2026-03-31T23:59:59

L'objectif de cette cotutelle de thèse est de concevoir des plateformes nanométriques pour le ciblage des tumeurs. Ces plateformes sont basées sur des nanoparticules d'or encapsulées dans des micelles fluorées polymérisées (pour le transport de l'oxygène) et portant un radiopharmaceutique (pour la thérapie et l'imagerie in vivo) et un anticorps ciblant les tumeurs. Un effet synergique est attendu en amplifiant l'effet du radiopharmaceutique grâce à l'or et aux espèces réactives de l'oxygène produites à partir de l'O2 dissous dans la phase fluorée de la micelle.

Over the past few years, medicine has been a field in which nanotechnologies have shown great promise particularly for diagnosis and drug-delivery applications. The challenge of nanomedicine consists in carrying active molecules through the different biological barriers and reaching specific targets in an efficient and nontoxic way. In addition, some active agents require specific formulations to overcome intrinsic problems associated with aqueous insolubility, in vivo stability, and bioavailability. With the advent of nanotechnologies, a whole range of new carriers with different properties and functionalities are now available. However, the development of small biocompatible carriers with high therapeutic efficacy, extended circulation time, and favourable biodistribution has several unanswered issues. Examples of nanometric delivery systems that are currently applied or under development include polymers, liposomes, lipid nanoparticles, dendrimers, carbon nanotubes, metallic nanoparticles, and micelles. Micelles are made of amphiphilic molecules consisting of two distinct regions with opposite affinities towards a given solvent (for example, water). They self-assemble as colloidal particles with a hydrophobic core and hydrophilic shell. When used as aqueous carriers, micelles can efficiently solubilize pharmaceuticals in their core.

Development of novel radiotherapeutic approches against cancer

The general work program will consist in the following main tasks:
1) Organic synthesis of fluorinated amphiphiles to be assembled into carriers with different surface chemistries and polymerized;
2) Synthesis of gold nanoparticles;
3) Characterization of the supra-molecular assemblies;
4) Complexation studies with 177Lu;
5) attachment of antibodies by click
6) Assessment of cytotoxicity by in vitro experiments with different cell lines (internalization pathways);
7) Evaluation of the encapsulated micelles as radiosensitizer;
8) Monitoring of biodistribution by in vivo imaging of the micellar carrier;
9) In vivo proof of concept for therapeutic applications.