A team led by University of Warwick researchers is using light to activate a cancer-killing compound that attacks a vital energy source in cancer cells. This technique could be used not only to treat cancer, but also to help reduce side effects of treatment and potentially immunize against developing the disease in the future. “There is an increasing interest in reducing the side effects of cancer treatment as much as possible, and anything that can be selective in what it targets will help with that,” said researcher Peter Sadler, a chemistry professor at Warwick. “If [cancer cells] have become resistant to other cancer drugs, they may not be resistant to this treatment because the way it kills the cancer cells is different.” Visible light can activate an iridium catalyst (large purple ball) with a special coating (gray balls) that homes in on coenzyme NADH (red/gray/purple balls at bottom) in cancer cells and removes an electron from them, thus destroying them by cutting off a vital energy source and generating a toxic form of oxygen (in the blue bubble). Courtesy of Huaiyi Huang, Sun Yat-Sen University. In current cancer treatment methods, photodynamic therapy (PDT) kills cancerous tumors in the body by activating a photosensitizer chemical compound, which creates species that can attack cancer cells in the presence of light. This allows clinicians to direct the light to specific regions of the tumor and, in the process, spare healthy tissue. Existing techniques rely mainly on the presence of oxygen, as many tumors are hypoxic — deficient in normal oxygen due to poor blood supplies. “The power of light to change the reactivity of chemical molecules dramatically within a thousandth of a millionth of a second can now be harnessed to treat resistant cancers," said researcher Vas Stavros, a professor of physical chemistry at Warwick. This new technique uses a compound of the metal Iridium that will kill cancer cells in culture even when oxygen concentration is low. The team found that once this compound is activated by light, it attacks the energy-producing machinery in the cancer cells — a vital co-enzyme called nicotinamide adenine dinucleotide (NADH). Cancer cells have a very high requirement for NADH because they need a lot of energy to divide and multiply rapidly. The new method “catalytically destroys that co-enzyme or changes it into its oxidized form.” This upsets the energy-producing machinery in a cancer cell and effectively cuts off the tumor's power source. “The compound that we have developed would not be very toxic at all. We would give it to the cancer cells, allow a little time for it to be taken up, then we irradiate it with light and activate it in those cells,” Sadler said. “We would expect killing of those cancer cells to occur very quickly compared with current methods." According to the researchers, the new technique can treat any tumors where light can be administered, namely bladder, lung, esophageal, brain, and skin cancers. In addition, the technique could potentially be used to immunize patients against future cancers because as such cells die, they change their chemistry in such a way that they will generate an immunotherapeutic response in the body. The team plans to continue investigating their technique’s immunization potential. “This breakthrough illustrates the power of modern computation to understand the effects of light on chemical molecules to provide drugs of the future with truly unique mechanisms of action,” said researcher Martin Paterson, a professor at Heriot-Watt University in Scotland and head of the school’s Chemical Sciences Research Institute. The research was published in Nature Chemistry (https://doi.org/10.1038/s41557-019-0328-4).