Cuproptosis is fundamentally different from all previously known mechanisms of cell death: The deciding trigger is an excess of copper in the cell.
It binds to certain proteins in the mitochondria that are normally responsible for energy production. These proteins clump together as a result, the cell undergoes extreme stress, and then it dies.
“What makes this type of cell death so unique is its specificity in targeting the cell’s energy production,” explains Karges.
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“Cancer cells often have an altered, particularly intense metabolism and take in more copper than healthy tissue does.”
Karges’ team has successfully developed a copper complex that selectively induces cuproptosis. It is approximately 100 times more effective than existing platinum derivatives currently used clinically.
“However, the substance was not selective at first and was fatal to healthy cells as well,” says Karges. “We were able to solve this issue by integrating the ingredient in light-activated nanoparticles.”
Packaging with dual benefits
The actual agent complex is embedded in polymeric nanoparticles. Due to the increased metabolism of cancer cells, these particles accumulate in tumours.
The agent is thus selectively transported to where it is supposed to take effect. In addition, the polymer coating prevents the copper complex from being prematurely and uncontrollably released.
A light stimulus is required to release the agent on site. “The release principle is based on a photo-responsive bond within the basic polymer framework,” says Karges.
“Light radiation selectively severs this specific bond, whereupon the nanoparticles dissolve, and the copper complex is released locally.” This allows highly precise and selective treatment of cancer cells.
“We were also able to show that this method is effective in treatment-resistant cancer cells, where conventional chemotherapy treatments hit their limits.”
However, much research must still be done before the method can be used clinically. “So far, we have shown this on resistant cancer cells in the lab, not in a human body,” Karges emphasises. “A lot still has to be done before an actual treatment can be performed.”
Source: Ruhr-University Bochum
