Ruhr-University BochumNov 1 2024

Tumors often contain areas of oxygen-deficient tissue that frequently withstand conventional therapies. This is because the drugs applied in tumors require oxygen to be effective. An international research team has developed a novel mechanism of action that works without oxygen: polymeric incorporated nanocatalysts target the tumor tissue selectively and switch off the glutathione that the cells need to survive. The group headed by Dr. Johannes Karges from the Faculty of Chemistry and Biochemistry at Ruhr University Bochum, Germany, published their findings in the journal Nature Communications on October 31, 2024.

Why tumors shrink but don't disappear

"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."

Johannes Karges, Ruhr-University Bochum

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.

Compound accumulates in tumor tissue

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."

Source:

Ruhr-University Bochum

Journal reference:

Zhang, H., et al. (2024) Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma. Nature Communications. doi.org/10.1038/s41467-024-53646-y.