Towards Novel Inert (Photo-)toxic Ru(II) Polypyridyl Complexes

Informations projet

PhotoMedMet

N° de convention de subvention: 681679

DOI

10.3030/681679

Projet clôturé

Date de signature de la CE 30 Septembre 2016

Date de début 1 Octobre 2016

Date de fin 31 Mars 2022

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 000 000,00

Contribution de l’UE

€ 2 000 000,00

Coordonné par

ECOLE NATIONALE SUPERIEURE DE CHIMIE DE PARIS
France

Periodic Reporting for period 4 - PhotoMedMet (Towards Novel Inert (Photo-)toxic Ru(II) Polypyridyl Complexes)

Période du rapport: 2021-04-01 au 2022-03-31

Résumé du contexte et des objectifs généraux du projet

Cancer is still a leading causes of death in the world. Needless to say that is of utmost importance to uveil new chemotherapeutic agents or alternative medical treatment. In this project, we aim at tackling these problems using two different methods, namely 1) by preparing novel anticancer agents that can target specifically cancer cells and 2) by using a medical technique called Photodynamic Therapy (PDT) that allows activating a non-toxic drug at a certain location and time thanks to the use of light.

In both projects, due to their specific physico-chemical properties, ruthenium polypyridyl complexes were mainly used.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The main achievements made during this project are:
1) Discovery of a ruthenium-based compound that is about 75 more active on cancer cells that one of the main compounds that is currently given to patients (cisplatin).
2) Discovery of the ability of a ruthenium-based compound to extend the life of mice with a tumour.
3) Discovery of the relationship between the redox potential of our new ruthenium complexes and their biological activity.
4) Discovery of extremely potent ruthenium-based photosensitizers for PDT that absorb at about 600 nm.
5) Ability to couple ruthenium-based photosensitizers to antibodies to create new bioconjugates that accumulate better in cancer cells than in healthy cells.
6) Possibility to improve the tumour uptake of a ruthenium-based drug candidate by 18 times thanks to the encapsulation into a biocompatible and biodegradable polymer.
7) Discovery of ruthenium complexes that can be activated at 800 nm thanks to 2-photon irradiation. The compound is active in vivo.
8) Discovery of an osmium complex that can be activated at 740 nm thanks to 1-photon irradiation. The compound is active in vivo.

Overall, this project has been extremely successful with about 100 articles published thanking the ERC. In addition, 3 patent applications were filed and it is hoped, in vivo experiments depending, that this project could lead to the creation of a start-up. In addition, I had the opportunity to present the work resulting of this ERC grant 94 times at well-known Universities (Hong Kong University, UC San Francisco, Cambridge University, Oxford University, etc.) all around the world as well as at very important conferences.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The main progresses made during the course of this project that are beyond the state of the art are:
1) the preparation of ruthenium polypyridyl complexes that can be excited at 800 nm by 2-photon irradiation and that are extremely active in vivo.
2) the discovery of an osmium complex that can be excited at 740 nm by 1-photon irridation and that is extremely active in vivo.
3) the discovery of an extremely active ruthenium complex against cancer cells that are far more active than the reference compound cisplatin and that are active in vivo.
4) the discovery of an encapsulation method that allows delivering a ruthenium-based drug candidate to an ovarian cancer type of tumours extremely efficiently. An 18 time higher accumulation was observed.

Photodynamic Therapy Concept