At the University of Basel, researchers have built an iridium-based catalyst that can bind to cancer cells and switch on a drug at the tumor itself. The idea is to keep more of a chemotherapy medicine inactive until it reaches its intended target, potentially limiting the damage to healthy tissue.
Many chemotherapy drugs can harm fast-growing healthy cells as well as cancer cells. This can cause difficult side effects, including nausea and hair loss. A team led by Dr. Thomas Ward in the Department of Chemistry and the Swiss Nanoscience Institute is working on a different approach: use a carefully placed catalyst to turn an inactive drug, called a prodrug, into its active form near a tumor.
The researchers described their method in a study published in the Journal of the American Chemical Society. It uses a chemical process called a Buchner ring expansion. An iridium catalyst starts that process by changing an aromatic ring in the prodrug, which releases the active drug.
The catalyst is fitted with an inhibitor that attaches to a tumor protein called hCA IX. The inhibitor works like an address label. It helps the catalyst bind to cancer cells that have high levels of hCA IX on their surface. When the prodrug is then added, a chain of chemical steps releases the medicine at the cell. The team reports that the reaction is highly selective and can work at very low concentrations.
For their test, the researchers used epirubicin, a chemotherapy drug already in common use. Dr. Damian Graf, who carried out the work as part of the Swiss Nanoscience Institute Ph.D. School, said linking the catalyst to the hCA IX inhibitor helped confine the drug’s release to cancer cells.
The approach is still at an early research stage. It has not been shown to reduce side effects in patients, and the researchers say further testing in preclinical models is needed before the method can be prepared for clinical use. Those studies will help establish how well the system works in living organisms and whether it can move closer to human trials.
If the next steps go well, the method could offer a flexible way to deliver different medicines: the researchers say the catalyst can be paired with various active ingredients. The work may also contribute to bioorthogonal chemistry, a field that aims to carry out chemical reactions inside living systems without disrupting their natural processes. For now, the Basel team’s result is a proof of concept: a targeted chemical tool that activates a chemotherapy drug where it is meant to act, with its safety and usefulness still to be tested.