Project description
Novel photosensitisers for cancer photodynamic therapy
Photodynamic therapy is a promising type of cancer treatment that uses a photosensitiser, which accumulates in the target cell and after exposure to the specific type of light produces reactive oxygen to kill the cell. To improve effectiveness of the therapy, better photosensitisers are needed. The EU-funded OrganometRuPDT proposal plans to use cyclometalated Ru(II) polypyridyl complexes as novel photosensitisers in cancer photodynamic therapy. These compounds are easy to synthesise and they will have a higher lipophilicity, enabling better penetration through cell membranes. Researchers plan additional steps to increase specificity of these molecules and apply X-ray fluorescence and single cell inductively coupled plasma mass spectrometry to determine their biodistribution.
Objective
In this project, I plan to use cyclometalated Ru(II) polypyridyl complexes as novel photosensitizers (PSs) in photodynamic therapy (PDT) to fight cancer. Such compounds are easier to synthesise than the well-known porphyrins and have a higher lipophilicity (to better cross the cell membrane) and a bathochromic shift of the absorption (to irradiate at low energies) than the usual Ru(II) polypyridyl complexes. Furthermore, I plan to couple maleimide moieties to these complexes to directly bind cysteine-containing biomolecules (i.e. HSA) and therefore, overcome the selectivity issues observed for the typical PSs. The use of bisbenzimidazoles as ancillary ligands will allow to tune the properties of the complexes in view of having the most red-shifted absorption. Computational chemistry will be first used to design the complexes, and after the synthesis and complete characterization, biological experiments will be performed to evaluate their potential as PSs. A secondment under the supervision of Prof. Clotilde Policar will allow localizing the compounds prepared by the use of a synchrotron-based imaging technique (X-ray fluorescence) as well as single cell ICP-MS, which will help to detect the metal inside the cell and figure out the biodistribution of the complexes. The multidisciplinary scope of this work along with their innovative aspects to selectively cause death of cancerous cells, make it a ground-breaking proposal. In addition, working in one of the best universities of the world, under the supervision of Dr. Gilles Gasser and Prof. Clotilde Policar will promote my scientific career.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
75231 Paris
France