A device developed by chemists at Université de Montréal promises to improve the way a powerful cancer-fighting drug is administered to patients. By using nanoparticles to generate optical effects, this new technology will make it possible to determine almost immediately how much of the drug remains in a patient’s bloodstream, a measurement that currently takes about half an hour. “Using this approach you can get a response in a couple of minutes, depending on the concentration,” says UdeM chemistry professor Jean-François Masson.
Such speedy results could matter significantly to an individual taking the common anti-cancer drug methotrexate, a highly toxic agent that can easily damage the body’s healthy cells. It is vital to take accurate, ongoing measurements to determine how much is present. Quick feedback will minimize the possibility of an overdose, while ensuring that there is enough methotrexate to tackle the cancer.
Methotrexate works by blocking the action of a key enzyme, dihydrofolate reductase (DHFR), which cancer cells require to thrive. Monitoring of this process has traditionally been conducted by adding to the patient’s blood sample a fluorescent version of the drug, which will compete with the unlabelled version for binding to an antibody. The resulting change in fluorescence polarization then demonstrates the amount of methotrexate that is present.
The alternative to this method was designed by Masson and a chemistry colleague Joelle Pelletier, who specializes in the catalytic behaviour of DHFR and other enzymes. The pair developed a mechanism that features a coating of gold nanoparticles on the surface of a receptacle containing the patient’s blood sample. Like methotrexate, these particles also block DHFR; as they compete with the drug they alter the colour of light passing through the sample. Different colours reflect varying concentrations of the drug.
The necessary equipment for this analysis is highly portable and costs about $10,000 — a small fraction of the cost of hardware currently used to track methotrexate. The original goal of the work was primarily a proof of principle, says Masson. However, after being approached by clinicians, “we really started to push forward to analyze clinical samples from patients.” He is also considering commercializing the technology.