Swiss chemists design catalyst to switch on chemotherapy drug at tumour cells
University of Basel researchers have built an iridium catalyst that seeks out cancer cells and activates a chemotherapy prodrug there, pointing towards gentler, more precise treatment in future.
Chemists at the University of Basel have developed a way to activate a chemotherapy drug only when it reaches cancer cells, a step towards treatment that leaves healthy tissue alone. The work comes from the group of Dr Thomas Ward, based in the university’s Department of Chemistry and the Swiss Nanoscience Institute.
The aim is to ease a well-known problem. Standard chemotherapy tends to hit healthy cells as well as tumours, which is why patients can be left with unpleasant effects including nausea and hair loss.
The Basel approach is rather neat. The team uses artificial metal compounds as catalysts that latch on to tumour cells. A “prodrug”, which is a medicine held in an inactive, caged form, is then converted into its working form right at the tumour.
The catalyst is built around iridium and carries an inhibitor of a tumour protein called hCA IX. That inhibitor works rather like an address label, guiding the catalyst to cells with plenty of the protein on their surface. Once the catalyst is in place and the prodrug is added, a chain of reactions enlarges an aromatic ring in the prodrug and frees the active medicine. Chemists call this a Buchner ring expansion. It picks its target with precision and needs only tiny amounts of catalyst.
To put the idea through its paces, the researchers used epirubicin, a widely used chemotherapy agent. Dr Damian Graf, who did the work through the Swiss Nanoscience Institute’s PhD School, said that attaching the hCA IX inhibitor allowed the team to keep the drug’s release confined to cancer cells. The study was reported in a journal from the American Chemical Society.
It is important to be clear about the stage reached. This is early laboratory research and has not yet been tested in people. The team’s next job is further work in preclinical models, ahead of any use in patients.
There is room for the idea to grow. The catalyst can be combined with a range of active ingredients, so the method is flexible. It could also feed into bioorthogonal chemistry, a growing field that carries out chemical reactions inside living systems without upsetting their natural processes.
Why it matters
Delivering a powerful drug where it is needed, and nowhere else, has long been a goal in cancer medicine, because damage to healthy tissue is what makes many treatments so gruelling. This work is still a long way from the clinic, but if it stands up to further testing, it could help make therapies more precise and less toxic for patients.
