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Light-activatable ruthenium-based anticancer prodrugs

Objective

Chemotherapy is, after surgery, the second most efficient therapy against cancer. However, it has many side effects for cancer patients because anticancer drugs kill cancer cells but also healthy ones. My project aims at synthesizing new metal-containing compounds that 1) are poorly toxic in the dark; 2) can be attached via a light-sensitive bond to liposomes that will carry them into cancer cells; and 3) detach from their carriers and become toxic upon light irradiation, thus killing cancer cells.

These new compounds contain ruthenium, a metal combining photochemical and anticancer properties. I will replace the weakly bound chloride ligands of known cytotoxic ruthenium compounds by strongly bound sulfur ligands. By doing so, the DNA- and protein-binding ability of the ruthenium compounds will be lowered, which will lower their toxicity in the dark. Thioether-lipid conjugates will be used to attach the ruthenium prodrugs to liposomes carriers that are well taken up by cancer cells.

Techniques to irradiate tumors in vivo are nowadays available in the clinics. By shining light onto the ruthenium-enriched cancer cells photochemical cleavage of the Ru-S bond will take place, thus detaching the metal complex from its carrier and allowing it for binding to biological molecules. Thus, the ruthenium prodrug will be transformed inside cancer cells into a highly toxic molecule that will kill the cells. I will study mononuclear compounds and molecules containing several ruthenium centres; visible light activation and near infrared light activation. The final aim is to obtain ruthenium-functionalized liposomes that are poorly toxic in the dark, preferentially go into cancer cells, and become toxic at the place of irradiation, using light that penetrates well into biological tissues.

Because of this unique combination of properties my new light-activatable ruthenium prodrugs will ultimately lead to selective anticancer treatment showing low side effects for cancer patients.

Field of science

  • /medical and health sciences/clinical medicine/surgery
  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds
  • /medical and health sciences/clinical medicine/oncology/cancer

Call for proposal

ERC-2012-StG_20111012
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITEIT LEIDEN
Address
Rapenburg 70
2311 EZ Leiden
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 418 400
Principal investigator
Sylvestre Bonnet (Dr.)
Administrative Contact
Ton Brouwer (Mr.)

Beneficiaries (1)

UNIVERSITEIT LEIDEN
Netherlands
EU contribution
€ 1 418 400
Address
Rapenburg 70
2311 EZ Leiden
Activity type
Higher or Secondary Education Establishments
Principal investigator
Sylvestre Bonnet (Dr.)
Administrative Contact
Ton Brouwer (Mr.)