Light-activated drugs could kill cancer with fewer side effects

Light-activated cancer drugs that don’t cause the toxic side effects of current chemotherapy treatments are closer to becoming a reality, a new study suggests.

Researchers say they now know more about how a pioneering platinum-based chemotherapy drug candidate—trans,trans,trans-[Pt(N3)2(OH)2(py)2]—functions when activated by light.

“The current shortcomings of most chemotherapeutic agents are unfortunately undeniable…”

The treatment is an inorganic-metal compound with an unusual mechanism, which kills cancer cells in specific targeted areas, in an effort to minimize toxic side effects on healthy tissue.

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

There is also a growing resistance to more traditional cancer therapies, so new treatments are needed, researchers say.

Completely inactive and non-toxic in the dark, scientists can insert the new treatment into cancerous areas and trigger its functions with directed light—causing the compound to degrade into active platinum and releasing ligand molecules to attack cancer cells.

“The current shortcomings of most chemotherapeutic agents are unfortunately undeniable, and therefore there is ongoing effort to develop new therapies and improve our understanding of how these agents work in effort to develop not only more effective, but also more selective, therapies to reduce the burden on patients,” says lead author Robbin Vernooij, a joint researcher from the Monash Warwick Alliance, a collaboration between the University of Warwick and Monash University.

“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,” Vernooij says.

Using an old spectroscopic technique—infrared spectroscopy—the researchers observed what happens to the structure of the compound by following the metal as well as molecules released from the compound.

The researchers shone infrared light on the inorganic-metal compound in the laboratory and measured the vibrations of its molecules as it was activated.

From this, they discovered the chemical and physical properties of the compound: some of the organic ligands, which are attached to the metal atoms of the compound, become detached and are replaced with water while other ligands remain stable around the metal.

This fresh insight into the mechanics of the treatment offers new hope that photoactive chemotherapy drug candidates, such as trans,trans,trans-[Pt(N3)2(OH)2(py)2], will move from the laboratory to future clinical trials.

“About half of all chemotherapy treatments for cancer currently use a platinum compound, but if we can introduce new platinum compounds that avoid side effects and are active against resistant cancers, that would be a major advance,” says Peter Sadler, professor of chemistry at the University of Warwick.

“Photoactivated platinum compounds offer such possibilities. They do not kill cells until irradiated with light, and the light can be directed to the tumor so avoiding unwanted damage to normal tissue.

“It is important that we understand how these new light-activated platinum compounds kill cancer cells. We believe they attack cancer cells in totally new ways and can combat resistance. Understanding at the molecular levels requires use of all the advanced technology that we can muster.

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



The researchers report their findings in Chemistry: A European JournalSource: University of Warwick, Posted by Luke Walton by University of Warwick, CC by 4,o International

Original Study DOI: 10.1002/chem.201705349