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In our bodies, fluctuations in the concentration of certain molecules can serve as early warning signals of a developing pathology, long before the first symptoms appear. Accurately quantifying the production of these molecules could enable the prevention of many diseases at very early stages.
The “Photoactive Materials and Bioimaging” team (University of Strasbourg – CNRS), led by Andrey Klymchenko in collaboration with Nobel Laureate Jean-Marie Lehn, has developed an innovative chemical concept for the rapid and efficient detection of some of the smallest molecules in our bodies: neurotransmitters. These chemical compounds, released by neurons, are indicators of brain health. Measuring their levels in patients’ blood or urine can help detect neurodegenerative diseases (such as Parkinson’s or Alzheimer’s), depressive disorders, or epileptic syndromes.
Andrey Klymchenko explains the uniqueness of this new method, published in January 2025 in Angewandte Chemie International Edition: “Currently, methods for measuring neurotransmitters in patients’ urine are cumbersome, requiring specialized laboratories and significant processing time. We have developed an artificial receptor concept that could, in the future, allow the simultaneous analysis of a large number of neurotransmitters within just a few minutes.“
Specialized in the design of fluorescent molecules and nanomaterials, the team has developed an ingenious supramolecular fluorescence-based system to measure dopamine, a neurotransmitter involved in numerous pathologies. “We designed a nanoscopic artificial receptor composed of a fluorescent molecule that emits red light. However, when it binds to a chemical group characteristic of neurotransmitters (in this case, dopamine), its structure changes, and the molecule emits blue light. This technique enables us to visualize and quantify dopamine concentration, but initially, it was not specific enough. We had to invent a system to ensure that only dopamine was recognized (and not other neurotransmitters).“
To achieve this, the researchers encapsulated the fluorescent molecules in nanoscopic lipid droplets, preventing neurotransmitters from penetrating without assistance. “This is where a ligand molecule comes into play—it specifically recognizes dopamine (like a key fitting into a lock) within the droplets and facilitates its passage inside, allowing it to bind to the fluorescent molecule.“
The researcher specifies that the experiment was conducted in the presence of numerous other neurotransmitters to test the specificity of the method:
“Only dopamine penetrates the droplets—this is a highly specific detection. We now have a validated proof of concept demonstrating the effectiveness of this new tool. The advantage of this method is that we will soon be able to test whether it works for other neurotransmitters by designing a specific receptor for each of them.”
More than just a diagnostic tool, this new technique could also be developed to visualize the specific production of each neurotransmitter directly within living organisms. The goal would be to better understand neuronal activity in animal models without the need for genetically modified organisms. These nanodroplets could be injected near neurons to be studied, allowing researchers to measure their activity via fluorescence microscopy and visualize the emitted neurotransmitters.
Developing this unprecedented technique was a clear high-risk bet. “It is difficult to obtain funding for developing a technique like this—we had no guarantee that it would work. With Prof. Jean-Marie Lehn, we were able to co-finance the PhD research of Bohdan Kozibroda, a brilliant student from the École Universitaire de Recherche en Chimie (SysChem), supported by the Foundation. Last year, my team also received substantial funding from the Foundation to develop this new concept. At every stage of this project, the Foundation has been there to support us in one way or another.”
As a winner of a Fondation Jean-Marie Lehn grant, Andrey Klymchenko now plans to explore the possibility of applying his method to other neurotransmitters. These funds will also allow him to improve the affinity of his receptor to achieve dopamine detection at lower, physiologically relevant concentrations.
In the medium term, the researcher does not hide his ambition to further develop this project. He is no stranger to innovation, having already founded two start-ups:
Fluorescent Artificial Receptor for Dopamine based on Molecular Recognition-driven Dynamic Covalent Chemistry in a Lipid Nanoreactor. Kozibroda, B., Lehn, M., & Klymchenko, A. S. Angewandte Chemie International Edition, 13 janvier 2025.
