PhD in chemistry (M/F) – Magnetically Activatable Nanoassemblies for Targeted Immunomodulation of Autoimmune Hepatitis

Autoimmune hepatitis is a chronic inflammatory liver disease currently treated with nonspecific immunosuppressive drugs, which are associated with substantial adverse effects and frequent relapses. This PhD project, conducted within the ANR-funded MAGNETIMA project, aims to develop multifunctional magnetic nanoassemblies combining iron oxide nanoparticles, an anti-inflammatory or immunosuppressive drug, and an antigenic peptide designed to promote antigen-specific immune tolerance.

Nanoassemblies with a hydrodynamic diameter of 50–60 nm will be prepared by flash nanoprecipitation and characterized to establish relationships between their composition, structural organization, stability, biodegradation, magnetic properties, and drug-release kinetics. The magnetic-core composition and alternating magnetic field parameters will be optimized to achieve controlled drug release under conditions compatible with biological environments.

Magnetic Particle Imaging (MPI) will be used to quantify the nanoassemblies, detect changes associated with their disassembly or degradation, and monitor their pharmacokinetics and biodistribution. The selected formulations will subsequently be evaluated by the consortium partners using human macrophage models, three-dimensional hepatic models, and a murine model of autoimmune hepatitis.

The main challenge is to overcome the limitations of systemic immunosuppression by developing a strategy that acts locally in the liver and combines two complementary mechanisms: anti-inflammatory activity triggered by an alternating magnetic field and the induction of antigen-specific immune tolerance.

Several scientific and technological barriers will need to be addressed. The project must produce 50–60 nm nanoassemblies that are sufficiently stable in biological environments while retaining the ability to disassemble in a controlled manner. It must also achieve reproducible magnetically triggered drug release, control the density and integrity of the antigenic peptide, and relate the physicochemical transformations of the nanoassemblies to their biological fate and immunological effects.

A major methodological challenge will be to determine whether MPI can provide information not only on the amount and localization of iron oxide nanoparticles, but also on their assembly state, degradation, and drug-release process. Ultimately, the project aims to provide preclinical proof of concept for precision magnetic immunomodulation in autoimmune hepatitis, with potential applications to other immune-mediated diseases.

Applicants should hold a Master’s degree or an engineering degree in chemistry, physical chemistry, materials science, nanoscience, chemical biology, formulation science, or a closely related field.

A strong background in physical chemistry and an interest in colloidal systems, nanomedicine, and research at the interface between chemistry, physics, and biology are expected. Previous experience in formulation, nanoparticles, polymers, physicochemical characterization, HPLC, cell culture, magnetism, biomedical imaging, or quantitative data analysis would be advantageous. However, applicants are not expected to have prior expertise in all these areas.

The successful candidate should demonstrate experimental rigour, the ability to develop scientific autonomy, intellectual curiosity, and an aptitude for analysing and integrating data obtained using complementary techniques. Good scientific English, an ability to work in an interdisciplinary consortium, and availability for research visits and experimental campaigns in Caen will be required. Previous experience in MPI or magnetic hyperthermia is not mandatory, as dedicated training will be provided during the PhD.