New ruthenium-based active agent enables cancer treatment in oxygen-depleted tumors

Most tumors grow so rapidly that vascular growth cannot keep up, and oxygen-depleted areas form within them. A new active agent could make it possible to treat them with photodynamic therapy.

Photodynamic treatment of cancer is based on administering an initially inactive substance that is only activated in the tumor via targeted light irradiation. It then generates reactive oxygen species that kill the cancer cells. However, this method reaches its limits when no oxygen is present, as is the case with many fast-growing tumors. Professor Johannes Karges’ research group at Ruhr University Bochum has achieved a breakthrough that makes the treatment of such tumors possible: When oxygen is absent, an alternative action mechanism comes into effect. This uses hydrogen peroxide, a natural metabolic product of the cells. The researchers report their findings in the Journal of the American Chemical Society from April 6, 2026.

An entirely new action mechanism

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."

Professor Johannes Karges, Ruhr University Bochum

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."