Photodynamic therapy, or PDT, is an established method for treating cancer and is widely used in clinical practice. Karges and his team have developed an entirely new action mechanism that functions independently of the oxygen concentration within the tissue: Light converts the ruthenium-based active agent into an excited electronic state. When oxygen is present, energy is transferred to molecular oxygen, creating singlet oxygen, which has a harmful effect on cells. “This process corresponds to the conventional, oxygen-dependent mechanism of photodynamic therapy,” says Karges.
When oxygen is absent, another mechanism comes into effect. The cause is the coordination of intracellular iron to the active agent. This interaction alters the electronic characteristics of the system such that instead of a transfer of energy, an ultra-fast, metal-to-metal transfer of electrons occurs from the excited ruthenium center to the iron center. The hydrogen peroxide is thereby converted into highly reactive hydroxyl radicals. “Because hydrogen peroxide is a natural metabolic product of the cell, this process can occur independently of the molecular oxygen,” explains Karges. The hydroxyl radicals that have formed cause oxidative damage to central cellular structures and thus kill the cancer cells.
This means that the substance remains active even under severe conditions where past therapies have failed. In the current study, the researchers demonstrated this with breast cancer cells. “This method can be used for many different types of tumors, in principle,” says Karges. “However, we have not yet begun trying this out with human subjects and are working to develop this.”
Experimental study
Cells
Exploiting Metal-to-Metal Electron Transfer in a Ru(II) Polypyridine–Deferasirox Conjugate for Hypoxic Photodynamic Therapy C