Light-activated platinum compound may improve chemotherapy

Kevin Robinson

A new platinum compound that can be activated by ultraviolet light to destroy tumors has been developed by researchers from the University of Warwick in Coventry, the University of Edinburgh, the University of Dundee, all in the UK, and from the Institute of Biophysics in the Czech Republic. The new compound may lead to more targeted treatment and could overcome the problem of resistance that often leads to the failure of chemotherapy to treat cancer.

A new light-activated platinum IV complex may help keep cancer cells from developing resistance to treatment.

Platinum derivatives are one of the most important classes of chemotherapy drugs and are very successful at treating a wide range of cancers. “They have a broad spectrum of antitumor activity and are particularly useful in testicular, ovarian, lung, bladder, esophageal, prostate, cervical and colon cancers, as well as cancers of the head and neck region,” said Peter J. Sadler of the University of Warwick.

The main problem with platinum, as with most chemotherapy drugs, is that it is administered systemically, usually orally or intravenously. That exposes both healthy and cancerous tissues to the treatment and leads to unpleasant side effects such as nausea, hair loss and sores. At the same time, the cancerous tissue builds up a resistance to the drugs. Eventually, there is a point at which healthy tissue can no longer withstand the onslaught of chemotherapy and the treatment must stop, regardless of whether the cancer has been eradicated.

Sadler and his colleagues have shown that, in identical conditions, the new compound, light-activated PtIV complex 1, is as effective or more so than cisplatin, a leading platinum-based chemotherapy drug. “Importantly, the complex was either nontoxic or much less toxic than cisplatin when it was not photoactivated,” he explained.

The researchers also studied how the complex affected DNA binding in human cells and in cell-free systems. They demonstrated that the complex formed distinct DNA-adducts compared with cisplatin. That implies differences in their mechanisms of action, which could explain its increased efficacy in the tumor cell lines, Sadler added. “This is an encouraging finding, as an advantage of light-activated chemotherapy over conventional chemotherapy or radiotherapy is the ability to retreat as often as desired over a period of years, if necessary.” The group has begun work to establish the pharmacokinetics, tissue distribution and efficacy of the complex.

As with other light-activated cancer therapies, getting light to the cancerous tissue poses an additional challenge to delivering the treatment. Sadler said that this particular complex, and others like it, can be activated by UVA and longer wavelengths of light, up to 520 nm, which can be useful for treating flat superficial lesions, particularly in hollow organs such as the bladder or esophagus. Thicker, nodular tumors would require more penetrating wavelengths for effective treatment.

Sadler said that the group continues to work on new complexes that can be activated by a range of wavelengths, new optics for multiphoton activation and photonic crystal fibers. The goal, he explained, is to develop a light-activated platinum complex for clinical trials and to demonstrate that the technology can be tuned for organ-specific indications.

PNAS, Dec. 26, 2007, pp. 20743-20748.