Watching enzymes work in vivo with rare-earth-based molecular probes

Scientists at the CNRS Centre de Biophysique Moléculaire (CBM) in Orléans and the Institut de Chimie des Substances Naturelles (CNRS/Université Paris-Saclay) have designed luminescent probes. They are based on complexes of lanthanides (Ln), a series of rare-earth metals whose trivalent Ln3+ ions are luminescent. The special feature of these probes is that the activity of certain enzymes can modify their luminescence in the near infrared, as well as the signal observed on MRI. These probes make it possible to track the catalytic activity of an enzyme with a single molecule using several complementary imaging techniques: MRI and near-infrared optics. Essential for unambiguous detection of a biological phenomenon, this dual imaging with a single molecule avoids biases due to the use of chemically different imaging agents for each imaging technique.

This study, published in the journal Angewandte Chemie International Edition, paves the way for new non-invasive diagnostic strategies.

This work has been reported on the Cnrs Chimie website

Article reference
Lanthanide-Based Probes for Imaging Detection of Enzyme Activities by NIR Luminescence, T1- and ParaCEST MRI
Rémy Jouclas, Sophie Laine, Svetlana V. Eliseeva, Jérémie Mandel, Frédéric Szeremeta, Pascal Retailleau, Jiefang He, Jean-Francois Gallard, Agnès Pallier, Célia S. Bonnet, Stéphane Petoud, Philippe Durand & Éva Tóth
Angew. Chem. Int. Ed. 2024
https://onlinelibrary.wiley.com/doi/10.1002/anie.202317728

La ligue contre le Cancer (The League Against Cancer) supports research carried out at the CBM

Each year, the Grand Ouest Committee of the League Against Cancer actively participates in research by financing a certain number of scientific projects. At the start of 2024, he donated €84,000 to CBM researchers.

3 projects, at the cutting edge of cancer research, have been funded.

"New therapeutic approach in oncology: development of PROTACs targeting LIMK1 and LIMK2 kinases"
Leader: Béatrice Vallée co-leader of the “Cell signaling and neurofibromatosis” team
Partner: Karen Plé, ICOA, UMR7311, CNRS/University of Orléans

The protein kinases, LIMK1 and LIMK2, are involved in cell skeletal remo Their active role in the development of cancers has been shown both in the formation of tumors and in their dissemination and the growth of metastases. Targeting LIMK1 and LIMK2 to develop new anti-cancer therapies is therefore a very relevant strategy.Unfortunately, traditional small chemical molecules inhibiting the activity of LIMK1 and LIMK2 have not passed clinical trials.In our project, we therefore decided to develop a new class of molecules, PROTACs, which allow the destruction of their target directly in the cell. In our case, we target the destruction of LIMK1 and LIMK2 to annihilate their oncological activity. This PROTAC strategy is very innovative and growing. Building on very promising results that have been obtained on other therapeutic targets, we hope to demonstrate the proof of concept of this new approach targeting LIMK1 and LIMK2, and thus open the way to new therapeutic molecules.

This project received the support of the League against Cancer, the Committees of Loiret, Loir-et-Cher and Morbihan, for the sum of €32,000.

“Innovative prostate cancer diagnosis for personalized medicine approaches: intelligent multiplex mapping of SKCa channels using near-infrared emitting lanthanide-based metallacrowns”
Leader: Svetlana ELISEEVA, “Luminescent lanthanide compounds, spectroscopy and optical bioimaging” team

Each patient's tumors are different because each individual is different. It is therefore crucial to take this diversity of tumors into account to develop personalized approaches. Our research work aims to characterize cancerous tumors with the aim of providing more effective treatment to cure cancer.Several specific potassium channels play a major role in the progression of cancerous tumors and are sensitive to therapies. In this project, we are implementing an innovative near-infrared optical imaging approach which will make it possible to establish the precise identity map of these potassium channels for each patient in order to provide personalized treatment.

This project received the support of the League against Cancer of the Committees of Loiret, Loir-et-Cher and Sarthe, for the sum of €30,000.

“Cancer immunotherapy: evaluation of synthetic versus in-cell expressed bispecific di-affibodies”
Leader: Josef Hamacek, head of the “Molecular assemblies and complex systems” team
Partners: Federico Perche, Vincent Aucagne (CBM), Florence Velge-Roussel (NMNS Tours)

Several receptors on the surface of cancer cells may represent potential targets for antibodies with broad neutralization spectrum. The principle of bispecific synergistic antibodies is to bind via a binding site on the surface of the tumor cell and with the other site to a receptor on the surface of the immune effector cell (NK, T lymphocytes).In this context, antibodies can be replaced by affibodies (AfBs) presenting affinities and selectivities for their targets comparable to antibodies, but having smaller size.This project aims to develop bispecific di-AfBs as innovative agents for the diagnosis and immunotherapy of cancer.These complex molecules are made up of two AfBs linked by linkers and can thus target two epitopes. AfBs will bind specifically to the corresponding receptors overexpressed on the surface of cancer cells to block signaling pathways, and to promote the recruitment of effector cells.This concept offers new therapeutic perspectives and makes it possible to optimize interactions with the cell and provoke the immune reaction.

This project received support from the League Against Cancer of the Committees of Loiret, Sarthe and Côtes d’Armor, for the sum of €22,000.

The League Against Cancer supports research carried out at the CBM and the INEM

The committees of the Grand Ouest Cancer League bringing together Brittany, Pays de la Loire, Centre-Val de Loire and Poitou-Charentes pool their resources to support cancer researchers.

On Tuesday 7 February at the CBM, La Ligue contre le cancer officially presented a check for €146,000 to support 6 teams of researchers from the CBM and the INEM (Laboratory of Experimental and Molecular Immunology and Neurogenetics). The projects supported aim to quickly achieve concrete results for the benefit of patients.

The committees of Loiret (represented by its volunteer Administrator, Doctor Jean-Louis Vaur) and Eure-et-Loir (represented by its volunteer Vice-President Mr. Jacques Dautreme) were present. The Loir-et-Cher, Cher and Morbihan committees, which are also funders, could not be present but indicated that they were happy to be able to contribute to the financing of regional research.

Mr. Jean-Marc Schneider from La République du Center came to immortalize this moment by going around the table allowing everyone to present their project as well as the benefits and progress to come.

Professor Vincent L. Pecoraro of the University of Michigan is invited at the CBM from May to August 2022 through a LE STUDIUM Research Professorship

Professor Pecoraro is internationally recognized for his major contributions in bioinorganic chemistry, notably on the role of manganese complexes and clusters in photosynthetic water oxidation. He is also a pioneer in the design of metalloenzyme mimetics and in the study of metallacrown complexes with unique magnetic and/or luminescence properties for developments in medical imaging, a field in which several patents have recently been filed with the team “Luminescent lanthanide compounds, optical spectroscopy and bioimaging” from the CBM.

Professor Pecoraro was awarded the Blaise Pascal International Chair in 2010. In 2021, he received an honorary doctorate from the University of Aix-Marseille and a LE STUDIUM Research Professorship (Loire Valley Institute). In addition, Professor Pecoraro is the 2021 recipient of the Franco-American award from the American Chemical Society and the “Société Chimique de France”.

He is currently president of the Society of Biological Inorganic Chemistry.

He is one of the co-founder of the startup VIEWaves founded in Orléans in March 2022 that aims at the commercialization of the optical imaging agents emitting in the near-Infrared domain created on the basis of the collaborative work conducted with the team at CBM.