Cancer killer in iridium attacks tumor power sources

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A new technique uses light to activate a cancer-killing compound in the metal iridium, researchers report.

The compound attacks a vital energy source in cancer cells even under hypoxia, significantly opening up the range of cancers that the technique can treat.

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

Works even in low-oxygen scenarios

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. The researchers 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 tumors where researchers can administer light, and would particularly suit treatments for bladder, lung, esophageal, brain, and skin cancers. There are around 10,000 bladder cancer cases in the UK alone per year, of which about 5,000 might potentially benefit from this kind of treatment.

“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,” says Peter Sadler, a professor in the chemistry department at the University of Warwick.

“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.”

Iridium compound attacks energy production

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 oxidized form. This upsets the energy-producing machinery in a cancer cell and effectively cuts off the tumor’s power source.

Our bodies need co-enzyme 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 note that as the cancer cells die, they change their chemistry in such a way that they will generate an immune reaction in the body, called an immunotherapeutic response. This suggests that those that get treatment with this technique might be immunized against attack from that cancer, something the researchers will investigate further.

“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,” says Vas Stavros, a professor of physical chemistry.

“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,” says Martin Paterson, a professor and head of the Chemical Sciences Research Institute at Heriot-Watt University.

“Now we have a potential new drug which can not only selectively kill cancer cells with normal oxygen supplies, but also hypoxic cancer cells which often resist treatment by photodynamic therapy,” says Hui Chao, a professor in the chemistry department at Sun Yat-Sen University.

“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,” adds Sadler.

Iridium was first discovered in 1803, and its name comes from the Latin for “rainbow.” From the same family as platinum, it is hard, brittle, and is the world’s most corrosion-resistant metal. Yellow in color, its melting point is more than 2,400° Celsius. It’s used in satellites and spacecraft due to its resistance to extreme environments. Scientists believe that a meteorite that wiped out the dinosaurs 66 million years ago enriched iridium in the Earth’s crust.

The paper appears in Nature Chemistry.

The Engineering and Physical Sciences Research Council (EPSRC), part of UK Research and Innovation, supported the research.

Source: University of Warwick