Tracking chemotherapy: New Research Enables Real-Time Monitoring of Drug Behavior in Cancer Cells
Researchers are developing a novel method to overcome limitations in assessing chemotherapy effectiveness and ensuring drug distribution within tumors. The approach involves chemically “tagging” chemotherapy drugs to allow for real-time tracking inside cells, perhaps paving the way for more personalized cancer therapies.
The research centers on a modified version of the widely used chemotherapy drug doxorubicin, now known as DOX-IR. This altered form of doxorubicin is designed to be detectable using infrared microscopy, a feat previously impossible with the drug in its standard form. The modification involves attaching a metal carbonyl – a chemical compound consisting of a metal atom bonded to carbon monoxide molecules – which acts as a traceable label by absorbing infrared light.
“Infrared spectroscopy can see doxorubicin’s chemical signature,but as it’s an organic molecule,its signal overlaps with that of cells. It’s very hard to distinguish those signals inside a cellular context,” explains Craig Richard, a postdoctoral research fellow at the Cancer Center at Illinois (CCIL). “When it’s labeled, though, it stands out very clearly because of that metal carbonyl group.”
The team, which also includes Pei-Hsuan Hsieh, Principal Scientist at Eli Lily and Company, compared the uptake of standard doxorubicin and DOX-IR in cancer cells. Their findings showed that cells absorbed DOX-IR over time, with the infrared signal increasing as the drug concentrated within the cells. Importantly, DOX-IR allows for the measurement of drug concentration within individual cells.
While promising, the research acknowledges current limitations. Richard notes that the addition of the infrared label alters the drug’s behavior. “Adding the infrared label changes how the drug behaves inside the cell. The modified drug doesn’t go to the same places as unmodified doxorubicin.” However, researchers are exploring solutions, such as engineering a linkage that breaks under specific conditions, to potentially restore the drug’s original activity while maintaining the infrared tracking capability.
despite this challenge, the development of DOX-IR offers notable potential. “This could have both therapeutic and diagnostic potential,” Richard stated. “You can take these metal carbonyls, and you can also give them signals to release the carbon monoxide that’s on them [metal carbonyls] and that can be used as a treatment for other diseases including cancer.”
The research provides a template for tracking other drugs and offers a new way to understand how chemotherapy drugs behave within cells, potentially identifying treatment effectiveness and resistance mechanisms.
The study,published in Analytical Chemistry (Hsieh,P.-H., et al.(2025). Monitoring Molecular Uptake and Cancer Cells’ Response by Development of quantitative Drug Derivative Probes for Chemical Imaging. Analytical Chemistry. doi.org/10.1021/acs.analchem.5c00863), was conducted at the University of Illinois Urbana-Champaign Cancer center at Illinois.
