New technique allows researchers to track chemotherapy drugs inside of cells

Scientists have made incredible progress in developing cancer therapies that help patients across cancer types. However, they face limitations in determining the results of drug effectiveness, as well as ensuring even distribution among all cancers cells because of the highly compact nature of tumors. Researchers are working to change that by giving chemotherapy drugs a kind of chemical ‘signal’ to track them inside cells.

This ground-breaking research focuses on a transformed version of a widely used chemotherapy drug, doxorubicin, which makes the previously undetectable drug, detectable.

The team driving this discovery includes Pei-Hsuan Hsieh, first author on the research team’s publication, a Tissue Microenvironment (TiME) Training Program alumna, and Principal Scientist at Eli Lilly, and Cancer Center at Illinois (CCIL) researchers Craig Richard, a postdoctoral research fellow, CCIL member Kannanganattu V. Prasanth, and CCIL Director Rohit Bhargava.

They’re using a version of doxorubicin also known as DOX-IR, which is modified by attaching a metal carbonyl, a chemical compound formed when a metal atom is bonded to one or more molecules of carbon monoxide, which acts as a labeled tracked device by absorbing infrared light, making it easy to detect the drug as it moves through cancer cells with an infrared microscope.

“Infrared spectroscopy can see doxorubicin’s chemical signature, but since it’s an organic molecule, its signal overlaps with that of cells,” said Richard. “It’s very hard to distinguish those signals inside a cellular context. When it’s labeled, though, it stands out very clearly because of that metal carbonyl group.”

In order to understand DOX-IR, researchers compared cancer cells that were treated with doxorubicin to DOX-IR. It was found that cells absorbed the DOX-IR over time and its signal increased as more of the drug was concentrated in cells. DOX-IR also allows them to measure drug concentration within a single cell. The promising result of the study paves the way for potential personalized cancer therapies.

“This could have both therapeutic and diagnostic potential,” Richard said. “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.”

As with any research, there are limitations in the current methodology of possibly using DOX-IR as a chemotherapy drug.

“Adding the infrared label changes how the drug behaves inside the cell,” said Richard. “The modified drug doesn’t go to the same places as unmodified doxorubicin. However, if you engineer a linkage that breaks under certain conditions, you could potentially restore doxorubicin’s normal activity while keeping the infrared label inside the cell.”

The use of infrared spectroscopy shows how this cancer drug behaves inside cells which can help determine treatment effectiveness and which cells are treatment resistant. “This gives researchers the template for how to do this with other drugs potentially,” said Richard.

Editor’s Notes:

This story was written by Hailee Munno, CCIL Communications Intern.

The paper “Monitoring Molecular Uptake and Cancer Cells’ Response by Development of Quantitative Drug Derivative Probes for Chemical Imaging” is published in Analytical Chemistry and is available online here: https://pubs.acs.org/doi/10.1021/acs.analchem.5c00863

Research reported in the publication was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health.