designed by Huaiyi Huang at Sun Yat-Sen University

A space-age metal that formed part of the asteroid that destroyed the dinosaurs could provide a new method of treating cancer tumours selectively using light.

Scientists at the University of Warwick in collaboration with Heriot Watt University and colleagues in China, France, Switzerland have developed a technique that uses light to activate a cancer-killing compound of Iridium that attacks, for the first time, 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 is detailed in a paper published on Monday, September 23 in Nature Chemistry and could lead to another tool for clinicians to use in the fight against cancer, and potentially even vaccinate patients against future cancers.

Photodynamic therapy (PDT) uses light to kill cancer tumours in the body by activating a chemical compound called a photosensitiser, 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 tumour and spare normal tissue from damage.

Current methods mainly rely on the presence of oxygen and many tumours are ‘hypoxic’, which means that they are deficient in normal oxygen often due to poor blood supplies. The international team of scientists have now 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 tumours where light can be administered, and would be particularly suited to treat bladder, lung, oesophageal, brain and skin cancers. There are around 10,000 bladder cancer cases in the UK per year, of which 5,000 would potentially benefit from this kind of treatment.

Professor Martin Paterson, Head of Chemical Sciences Research Institute at Heriot-Watt University commented: “This breakthrough illustrates the power of modern computation to understand the effects of light on molecules to provide drugs of the future with truly unique mechanisms of action.”

Professor Peter Sadler from the University of Warwick’s Department of Chemistry said: “All the time in cancer treatment, clinicians are trying to fight resistance. Drugs can kill the cancer cells initially, but with repeated treatment the cells become resistant, they learn how to chemically modify the drug or counteract its mechanism of action. Researchers are looking for novel ways in which the cancer cell will die. If they 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.

“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. 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 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 cells - a vital co-enzyme called nicotinamide adenine dinucleotide (NADH) - and catalytically destroys that co-enzyme or changes it into its oxidised form. This upsets the energy-producing machinery in a cancer cell and effectively cuts off the tumour’s power source.

Our bodies need coenzyme nicotinamide adenine dinucleotide (NADH) to generate energy. Cancer cells have a very high requirement for NADH, because 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 immunised against attack by that cancer, and will be investigated further in future research.

The paper, 'Targeted photoredox catalysis in cancer cells', is available online at https://www.nature.com/articles/s41557-019-0328-4

Image: Photo designed by Huaiyi Huang at Sun Yat-Sen University