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

Periodic Reporting for period 3 - PhotoMedMet (Towards Novel Inert (Photo-)toxic Ru(II) Polypyridyl Complexes)

Reporting period: 2019-10-01 to 2021-03-31

Cancer is still one of the leading causes of death in the world. Chemotherapy is one the medical techniques used to treat patients with cancer. Despite impressive progresses, chemotherapeutic agents are often far from ideal since patients undergoing such treatments often suffer from severe side-effects. In this project, we envisioned to tackle these drawbacks using two differents methods.
1) By preparing novel anticancer agents that can target specifically cancer cells.
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. This allows for a reduction of the side-effects since the drug is activated only when and where the medical doctor shines light.

More specifically, for both projects, we have decided to use a specific type of compounds called metal complexes to reach our goals. These metal complexes are based on ruthenium, a transition metal.
The main achievements so far of 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) Ability to improve the cellular uptake of ruthenium-based photosensitizers thanks to encapsulation into polymers.
The main progesses so far that are beyond the state of the art are

1) the preparation of ruthenium polypyridyl complexes that absorb at about 600 nm.
2) the discovery of extremely active ruthenium complexes against cancer cells that are far more active than the reference compound cisplatin.

The expected results are

1) filing of patents to protect our discoveries.
2) Allow our active Ru-based anticancer drug candidates to be brought specifically to cancer cells.
2) Confirm the ability of our Ru-based PSs to work in mice.