Spectroscopy Explores Photoinduced Reactions in Anticancer Drug

Using IR spectroscopy, researchers have gained fresh insight into how a platinum-based chemotherapy drug candidate functions when activated by light. Completely inactive and nontoxic in the dark, the treatment can be targeted to cancerous areas and is triggered only when directed light hits it, causing the compound to degrade into active platinum and releasing ligand molecules to attack cancer cells.

The photodecomposition mechanism of trans,trans,trans-[Pt(N₃)₂(OH)₂(py)₂] (1, py=pyridine), an anticancer prodrug candidate, was probed using complementary attenuated total reflection Fourier transform infrared (ATR-FTIR), transient electronic absorption, and UV/Vis spectroscopy.

Representation of light-activated cancer drugs. Courtesy of Robbin Vernooij/University of Warwick.

Researchers from the University of Warwick and Monash University used spectroscopy to follow the metal and the molecules released from the compound. The team shone IR light on the inorganic-metal compound in the laboratory and measured the vibrations of its molecules as it was activated. It found that some of the organic ligands, which were attached to the metal atoms of the compound, became detached and were replaced with water, while other ligands remained stable.

A better understanding of the mechanics of light-activated chemotherapy could help photoactive chemotherapy drug candidates progress from laboratory to clinical trial.

“This is an exciting step forward, demonstrating the power of vibrational spectroscopic techniques combined with modern computing to provide new insights on how this particular photoactive chemotherapeutic agent works, which brings us one step closer to our goal of making more selective and effective cancer treatments,” researcher Robbin Vernooij said.

“It is important that we understand how these new light-activated platinum compounds kill cancer cells,” professor Peter Sadler said. “We believe they attack cancer cells in totally new ways and can combat resistance.”

The majority of cancer patients who undergo chemotherapy treatment currently receive a platinum-based compound. These therapies, developed over a half-century ago, can cause toxic side effects in patients, attacking healthy as well as cancerous cells.

“We hope that new approaches involving the combination of light and chemotherapy can play a role in combatting the current shortcomings of cancer therapy and help save lives,” Sadler said.

The research was published in Chemistry: A European Journal (doi: 10.1002/chem.201705349).