POPCORN

Carbon monoxide is an important cell-signalling molecule with many potential therapeutic applications. However, a main difficulty with realizing this in a clinical setting, lies in the control of its release. CO-releasing molecules (CORMs) represent a promising way towards achieving this goal but their clinical applications have been hampered by issues such as the toxicity of the metallic post-release products. In this project, we build on our strong experience in the design, synthesis, and imaging of metal carbonyl complexes to make the design of photoCORM drugs evolve to give a safer and more efficient CO photorelease. We have three main objectives that are tackled by innovative approaches. To address the issue of reactive metal toxicity we propose new designs and the conjugation of photoCORMs with nanoparticles in stable constructs. The constructs are designed to stabilize the reactive metallic species after CO release. To understand and optimize the factors influencing the CO release efficiency of the drug in the cells we propose to monitor the photorelease of CO in a biological context, by using a state-of-the-art approach combining light irradiation, synchrotron FTIR microspectroscopy, imaging methods and microfluidics to follow the release kinetic of CO directly inside living cells. To evaluate the toxicity of the new CORMs, we want to monitor the fate of CORMs after CO release by analytical approaches combining biological activity with quantification and mapping of the metallic species in cells.