Iridium catalyst activates chemotherapy drug directly at targeted cancer cells

Iridium catalyst activates chemotherapy drug directly at targeted cancer cells Lisa Lock Scientific Editor Andrew Zinin Chief Editor Conventional chemotherapy treatments often attack not only cancer cells but also healthy tissue, leading to severe side effects such as hair loss or nausea. The team led by Dr. Thomas Ward from the Department of Chemistry and the Swiss Nanoscience Institute (SNI) at the University of Basel is therefore pursuing an approach that uses artificial metal compounds as catalysts that specifically bind to tumor cells and then convert so-called prodrugs into the active ingredient at the tumor site. Artificial chemical reaction In their study recently published in the Journal of the American Chemical Society, the researchers presented the so-called Buchner ring expansion to convert the caged drug into the active drug. This is made possible by the use of a specific iridium-based catalyst designed to specifically bind to tumor cells. The iridium catalyst is functionalized with an inhibitor for a tumor protein (hCA IX). The inhibitor essentially acts as an address label, causing the catalyst to selectively bind to tumor cells that overexpress hCA IX on their surface. Once the catalyst is bound to the tumor cell and a prodrug is added, a reaction cascade occurs: An aromatic ring in the prodrug is expanded, thereby releasing the active ingredient. This reaction is highly selective and works even at extremely low concentrations. "As part of the study, we tested the method with the active ingredient epirubicin, a commonly used chemotherapeutic agent," explains Dr. Damian Graf, who conducted this research as part of the SNI Ph.D. School. "By coupling the catalyst to an inhibitor of the tumor protein hCA IX, we were able to specifically confine the release of the active ingredient to cancer cells." Potential for the future The results open the door to a new generation of cancer therapies that are more precise, less invasive and less toxic. "In the long term, this technology could fundamentally change the way we treat cancer," explains Ward, who, along with his team, conducts research on organometallic compounds. "Since the catalyst can be combined with various active ingredients, the method offers a high degree of flexibility. It could also pave the way for further applications in so-called bioorthogonal chemistry—a growing field that enables chemical reactions in living systems without disrupting natural processes." The next steps for further development include additional testing in preclinical models to prepare the method for clinical use. Publication details Damian Alexander Graf et al., Catalytic Uncaging of Anticancer Drugs via a Buchner Ring Expansion, Journal of the American Chemical Society (2026). DOI: 10.1021/jacs.6c14207 Journal information: Journal of the American Chemical Society Provided by University of Basel