Novel compound for phototherapy kills vital energy source for cancer cells

The phototherapy technique could lead to another tool for clinicians to use in the fight against cancer, and potentially even vaccinate patients against future cancers.

Visible light can activate an iridium (large purple ball) catalyst, which has a special coating (gray balls) which homes in on coenzyme NADH (red/gray/purple balls at bottom) in cancer cells and removes an electron from it, so destroying them by cutting off a vital energy source and generating a toxic form of oxygen (in the blue bubble).
Visible light can activate an iridium (large purple ball) catalyst, which has a special coating (gray balls) which homes in on coenzyme NADH (red/gray/purple balls at bottom) in cancer cells and removes an electron from it, so destroying them by cutting off a vital energy source and generating a toxic form of oxygen (in the blue bubble).
Designed by Huaiyi Huang at Sun Yat-Sen University

A team of researchers at the University of Warwick (Coventry, England), in collaboration with colleagues at Sun Yat-Sen University (Guangdong, China), Shenzhen University (Shenzhen, China), PSL Research University (Paris, France), the University of Zurich (Zurich Switzerland), and Heriot-Watt University (Edinburgh, Scotland), has developed a phototherapy technique to activate a cancer-killing compound of iridium that attacks a vital energy source in cancer cells even under hypoxia, significantly opening up the range of cancers that can be treated using the technique.

The technique could lead to another tool for clinicians to use in the fight against cancer, and potentially even vaccinate patients against future cancers.

Phototherapy, also known as photodynamic therapy (PDT), uses light to kill cancer tumors in the body by activating a chemical compound called a photosensitizer, which creates species that can attack cancer cells in the presence of light. Using this method, clinicians can direct the light to specific regions of the cancer tumor and spare normal tissue from damage.

Current methods mainly rely on the presence of oxygen and many tumors are hypoxic, which means that they are deficient in normal oxygen often due to poor blood supplies. Recognizing this, the international research team developed a compound of the metal iridium that will kill cancer cells in culture, even when oxygen concentration is low.

The technique can treat any tumors where light can be administered, and would be particularly suited to treat bladder, lung, esophageal, brain, and skin cancers.

"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," says Professor Peter Sadler from the University of Warwick's Department of Chemistry. "The compound that we have developed would not be very toxic at allwe would give it to the cancer cells, allow a little time for it to be taken up, then we would irradiate it with light and activate it in those cells. We would expect killing of those cancer cells to occur very quickly compared with current methods." 

Once light-activated, the iridium compound attacks the energy-producing machinery in the cancer cellsa vital co-enzyme called nicotinamide adenine dinucleotide (NADH)—and 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. 

Our bodies need NADH to generate energycancer cells have a very high requirement for NADH, as they need a lot of energy to divide and multiple rapidly. 

The researchers even found that the compound still works in the presence of oxygen, by converting it into a 'toxic' type of oxygen that will kill the cancer cells.

The team of scientists also noted that as the cancer cells die, they change their chemistry in such a way that they will generate an immune reaction in the body, what is known as an immunotherapeutic response. This suggests that those treated by this technique might be immunized against attack by that cancer, and will be investigated further in future research.

"The ability of metal compounds to induce an immunogenic response in the body that may effectively vaccinate a person against future attack by cancer is an exciting development. It is very speculative, but we are looking further into the hallmarks of that," Sadler adds.

Full details of the work appear in the journal Nature Chemistry.

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