Nanoscale device optimises dose of toxic cancer drug

A miniature device developed at the University of Montreal can rapidly measure a patient’s blood for methotrexate, a commonly used but potentially toxic cancer drug. 

Claimed to be as accurate – and ten times less expensive – than equipment currently used in hospitals, this nanoscale device has an optical system that takes less than a minute to gauge the optimal dose of methotrexate a patient needs, while minimising the drug’s adverse effects.

The research was led by Jean-François Masson and Joelle Pelletier at the university’s Department of Chemistry.

Methotrexate has been used for many years to treat certain cancers, among other diseases, because of its ability to block the enzyme dihydrofolate reductase (DHFR). This enzyme is active in the synthesis of DNA precursors and promotes the proliferation of cancer cells.

‘While effective, methotrexate is also highly toxic and can damage the healthy cells of patients, hence the importance of closely monitoring the drug’s concentration in the serum of treated individuals to adjust the dosage,’ Masson said in a statement.

Until now, monitoring has been done in hospitals with a device using fluorescent bioassays to measure light polarisation produced by a drug sample.

‘The operation of the current device is based on a cumbersome, expensive platform that requires experienced personnel because of the many samples that need to be manipulated,’ Masson said.

Six years ago, Joelle Pelletier, a DHFR enzyme specialist, and Jean-François Masson, an expert in biomedical instrument design, investigated how to simplify the measurement of methotrexate concentration in patients.

Gold nanoparticles on the surface of the receptacle change the colour of the light detected by the instrument. The detected colour reflects the exact concentration of the drug in the blood sample. In the course of their research, they developed and manufactured a miniaturised device that works by surface plasmon resonance.

Roughly, it measures the concentration of serum (or blood) methotrexate through gold nanoparticles on the surface of a receptacle. In ‘competing’ with methotrexate to block the enzyme, the gold nanoparticles change the colour of the light detected by the instrument, with the colour of detected light reflecting the exact concentration of the drug in the blood sample.

The accuracy of the measurements taken by the new device were compared with those produced by equipment used at the Maisonneuve-Rosemont Hospital in Montreal.

‘Testing was conclusive: not only were the measurements as accurate, but our device took less than 60 seconds to produce results, compared to 30 minutes for current devices,’ Masson said.

In addition to producing results in real time, the device designed by Masson is small and portable and requires little manipulation of samples.

‘In the near future, we can foresee the device in doctors’ offices or even at the bedside, where patients would receive individualised and optimal doses while minimising the risk of complications,’ Masson said.

The device has economic benefits too.

‘While traditional equipment requires an investment of around $100,000, the new mobile device would likely cost ten times less, around $10,000.’