Photodynamics of photoactivated platinum anticancer agents

Since the discovery of anticancer properties of cisplatin in the 1960s, chemotherapy with platinum- based drugs became one of the main methods of cancer treatment. Platinum-based anticancer compounds have been effective against certain types of cancers, but show several disadvantages, one of which is the toxicity to both cancer and the surrounding healthy cells, causing severe side effects for the patients. Photodynamic therapy attempts to address this issue by using drugs which are activated with light selectively in the cancer tissue. While most photodynamic therapy agents convert upon light activation the surrounding oxygen and water into reactive oxygen species deadly for the cells, many tumours show low oxygen concentration, thus decreasing the efficiency of such therapy. Therefore, several compounds potentially suitable for photodynamic therapy with a different mechanism of action have been proposed in recent years. Light activated platinum compounds are among them. The development of anticancer drugs is very much hampered by the lack of understanding of their mechanisms of action. Although there is some knowledge about the mechanism of action of photoactivatable platinum complexes as a result of numerous experimental studies, a detailed insight into the processes occurring directly after the complex is excited by light is still missing. Such insights may be obtained with theoretical chemistry, and this is exactly what this project aims for. The ultimate goal of this project is to perform computer simulations with cutting edge theoretical chemistry methods of the processess occurring after light excitation in light activated platinum complexes and their reactions, including interactions with biomolecules, contributing to the understanding of the mechanism of action of these drugs and helping in improving their efficiency and selectivity towards cancer cells. The methodology required to perform these simulations will be developed and implemented in a program. The first part of the project will be carried out at the ETH Zurich in Switzerland in the group of Prof. Markus Reiher, and the second part in the group of Prof. Leticia Gonzlez at the University of Vienna. The project will have an impact beyond platinum complexes or photodynamic therapy, as the developed methodology may be used for simulating photoprocesses in any other metal complexes, and thus would help understanding many other photochemical mechanisms relevant for the cutting-edge research.

No additional funding sources recorded.