Theranostics Nano-vectors

We design fluorescent nanoparticles such as Gold Nanoclusters or organic dyes (Bodipy) that can be detected in the Near-Infrared windows such as NIR I (650-800 nm) or NIR II (900-1700 nm, also called SWIR) windows and using photoacoustic. We also develop nanoparticles that induce an imaging contrast upon X-ray irradiation, including nanoscintillators and activatable liposomes.

After specific accumulation in the tumor site(s), the overall idea is to activate these non-toxic agents to turn them into therapeutic compounds directly in the tumor site using remote activation including X-Rays, Neutrons or Light. The nanoparticles we are investigating include atomically precise metal nanoclusters, nanoscintillators, boron containing nanosystems or activatable liposomes. These NP can induce X-ray dose-enhancement (RDE), radiosensitization, boron neutron capture therapy (BNCT), photodynamic therapy (PDT) or radiotherapy-triggered drug release.

Tumor resistance and innovative therapies

Skin cancers are among the most common cancers and their number is constantly increasing. The use of inhibitors of BRAF (BRAFi) and MEK (MEKi) combinations can improve the survival of patients with metastatic melanoma. Unfortunately, the systematic acquisition of resistance mechanisms rapidly renders these treatments ineffective. It is therefore necessary to discover new therapeutic alternatives based on an integrated vision of the melanoma cells and their microenvironment, that form a complex microsystem. Membrane receptors such as IGF1R can cooperate with certain integrins in the mechanisms of tumor transformation, invasion and resistance to therapies. Our project consists in mapping the interaction networks that are established between IGF1R or other membrane receptors and integrins, in response to treatments, in BRAFi/MEKi sensitive or resistant melanoma cells. This allows the identification of new therapeutic targets, as well as molecules or combinations of molecules capable of countering the resistance of tumor cells. The impact of specific inhibitors of these therapeutic targets is analyzed in vitro, on reconstituted skin models, and finally in vivo on animal models. In parallel, the expression of identified key players is studied in patient samples, in order to establish correlations with clinicopathological data and response to treatments. This will help to propose new prognostic markers of response to currently used targeted therapies.

Medical devices

For diagnostic purposes we are involved in the development of LIBS (laser induced breakdown spectroscopy) elemental microscopy. This technique allows relative and quantitative imaging of any chemical tissue sections. Elemental maps can be obtained in particular for detection of metallic nanoparticles. In collaboration with researchers from the Institut Lumière Matière (Université Lyon 1), we are pushing this technology toward the hospital laboratories. We have initiated the world's first clinical trial based on the use of this LIBS technology (MEDICO-LIBS clinical trial, NCT03901196), for the analysis of lung tissue from patients with idiopathic lung diseases.

We also develop NIR imaging instruments for in vivo applications. The NIR I and more recently NIR II optical windows enable deep non-invasive fluorescence imaging, allowing us to probe physiological and molecular processes at high resolution. We initially developed preclinical and clinical NIR I imaging devices in collaboration with Fluoptics, LynRed or KaerLabs or CEA-LETI. These systems were evaluated in clinical trials (NCT04274309, NCT05318872 or NCT01982227). We are currently developing an in vivo SWIR set up for small animals that combines SWIR imaging and SWIR spectroscopy for a wide range of biomedical applications.

Finally, in partnership with Visualsonics/FujiFilm, we are developing different photoacoustic set-ups for preclinical imaging.