"As tumors grow very quickly, consume a lot of oxygen and their vascular growth can't necessarily keep pace, they often contain areas that are poorly supplied with oxygen," explains Johannes Karges. These areas, often in the center of the tumor, frequently survive treatment with conventional drugs, so that the tumor initially shrinks but doesn't disappear completely. This is because the therapeutic agents require oxygen to be effective.

The mechanism of action developed by Karges' team works without oxygen. "It's a catalyst based on the element ruthenium, which oxidizes the naturally present glutathione in the cancer cells and switches it off," explains Karges. Glutathione is essential for the survival of cells and protects them from a wide range of different factors. If it ceases to be effective, the cell deteriorates.

All cells of the body need and contain glutathione. However, the catalyst has a selective effect on cancer cells as it is packaged in polymeric nanoparticles that accumulate specifically in the tumor tissue. Experiments on cancer cells and on mice with human tumors, that were considered incurable, proved successful. "These are encouraging results that need to be confirmed in further studies," concludes Johannes Karges. "Still, there's a lot of research work to be done before it can be used in humans."

Zhang H, Montesdeoca N, Tang D, Liang G, Cui M, Xu C, Servos LM, Bing T, Papadopoulos Z, Shen M, Xiao H, Yu Y, Karges J.
Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma.
Nat Commun. 2024 Oct 31;15(1):9405. doi: 10.1038/s41467-024-53646-y