OrganometRuPDT | Cancer-Cell Specific Organometallic Ru(II) Complexes as Photosensitizers in Photodynamic Therapy

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/839499
Start date: 01-03-2020
End date: 15-07-2021
Total budget - Public funding: 107 746,24 Euro - 107 746,00 Euro
Cordis data

Original description

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.

Status

CLOSED

Call topic

MSCA-IF-2018

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2018
MSCA-IF-2018