The LANTEN project at the interface of chemistry, physics and biology, aims to design new lanthanide luminescent bioprobes (LLB) for two-photon (2P) microscopy bioimaging and simultaneously explores unprecedented diagnostic applications. The main originality of these probes is to target new biological transparency windows in the NIR (900-1300 nm) enabling in depth imaging. Three work-packages are envisaged: (WP1) the new 2P-LLBs will be designed to combine both two-photon absorption and optimized emission in the NIR spectral range, and fully characterized using advanced nonlinear spectroscopy techniques. The potential of these 2P-LLBs for 2P-microscopy bioimaging will then be evaluated in diffusive media, model of thick tissues then in cellulo and finally in vivo using zebrafish embryos. (WP2) The best NIR-2P-LLBs will then be functionalized by a reacting functionality enabling a specific encoding via peptide bioconjugation for cell internalization and organelle targeting. The main objective is to establish the proof-of-concept of tumour detection directly implemented in zebrafish embryo using NIR-2P-microscopy. (WP3) Finally, responsive NIR-antenna will be developed to be also sensitive to endogenous analytes acting as stimuli and fully characterized using nonlinear spectroscopy and in cellulo microscopy. The LANTEN project is based on a competitive consortium that combines the complementary skills required to overcome the challenges that represent (i) the synthesis of such advanced molecular probes as well as (ii) the intrinsic instrumental difficulties of NIR spectroscopy and microscopy. Overall, the final objective of the project is to provide new preclinical tools for in vivo diagnostic that will open up new perspectives for industrial applications in biology or medicine.

CONFI-Cat develops the design and the elaboration of innovative hybrid catalysts for selective and stable CO2 electroreduction. The reactivity and stability of the molecular catalysts are controlled by encapsulation. Molecular cages are used as matrices to structure, modify and control the local environment of the molecular electrocatalysts. Mechanistic studies, aimed at identifying the factors governing catalytic activity and selectivity, will complement the experimental developments. The final objective of the project is to develop innovative breathing electrodes based on carbon nanomaterials and cage/electrocatalyst composites for the efficient electroreduction of CO2.

CATHOMIX explores the harnessing of living, free and renewable electroactive microbial catalysts as mixed biofilms on biocompatible cathodes efficiently delivering electrons directly or in the form of H2 to a N2 fixing metabolism (the biological reduction of N2 to ammonia NH3). The ultimate objective of the project is to characterize and demonstrate in the laboratory the generation of ammonium (NH4+) at a microbial cathode powered with renewable electricity while using the microbial catalysed oxidation of waste at the anode of the device. At the cathode, the reduction of H2O to H2 is catalyzed by designed inorganic or biomimetic electrocatalysts based on non-noble metals. The cathode will be colonized with a mixed biofilm selected and enriched to target the fixation of N2 by the direct use of electrons or indirectly through electrogenerated dihydrogen. CATHOMIX will cross TRL 1-2 to TRL 3-4. The intermittence of power on energy efficiency and microbial ecology will be studied, quantified, modelled and managed.

The project aims to develop new radiopharmaceutical tools for theranostic in nuclear medicine, i.e. for therapeutic and diagnostic applications with a same molecular object. To ensure the specific delivery of the radionuclide to the tumor, the radiometal, that is confined in a chelator, must be coupled to a disease-specific targeting vector. Cyclic peptides are highly attractive as biovectors (advantageous pharmacokinetics, high penetration into tumor tissue, high metabolic stability and target affinity) but their potential for radiopharmaceutical development has not extensively been explored to date. The idea is to use metals polyazamacrocyclic chelators like tacn that will be incorporated in the bicyclic peptides in an innovative way in order to furnish original radiolabeled conjugates. To obtain important insights into the interplay between the metal chelator, tether(s), and cyclic peptide(s), a series of conjugates will be prepared and their biological properties assessed (receptor affinity and metabolic stability) in cell experiments. After further structural optimization, the biodistribution of the most promising candidates will then be assessed in small-animal experiments including PET imaging. The feasibility of this new approach will be demonstrated by following anticipated steps skillfully shared between the two partners: 1) chemical modifications of metal chelators for their subsequent incorporation in the peptides; 2) insertion of the chelators in the bicyclic peptides; 3) radiolabeling and characterization of non-radioactive metal complexes of bicyclic peptide conjugates; 4) in vitro characterization of radiopharmaceuticals; 5) preliminary in vivo evaluations of selected bicyclic peptide conjugates.

MARCEL 2.0 proposes an original concept where metallic nanocatalysts (Au, Ag, Cu nanoparticles) are functionalized with molecular hosting cavities bearing metallic complexes in order to direct the reactivity in ORR and CO2RR electrocatalysis. Both of these processes are complex and require efficient and highly selective catalysts as the metalloenzymes. Inspired form such biological systems whose functioning is based on confinement and supramolecular effects, MARCEL seeks the rational control of forming and stabilizing intermediates to guide specific reaction pathways. This innovative design that relies on surface supramolecular effects will be further combined to plasmonic effect in order to enhance the electrocatalytic performance. The reactivity and interfacial phenomena will be thoroughly investigated by combining experimental (electrochemistry, in situ spectroscopies) and computational analyses.