Photodynamic therapy (PDT) uses light to destroy tumours by activating a photosensitive drug that creates reactive oxygen species that attack cancer cells. This process, however, relies on the presence of oxygen; and many tumours are hypoxic. Now, an international research team has developed a technique based on a light-activated iridium compound that kills in vitro cancer cells, even when oxygen concentration is low (Nature Chem. 10.1038/s41557-019-0328-4).
The new PDT approach – developed by researchers from the University of Warwick in collaboration with colleagues from Sun Yat-sen University, Shenzhen University, the University of Zurich, Heriot-Watt University and CNRS – expands the range of cancers that can be treated. PDT itself is suitable for treating tumours in any regions where light can reach, for example bladder, lung, oesophageal, brain and skin cancers.
The key difference between conventional PDT and the iridium-based approach lies in the mechanism by which the tumour cells are killed. Once light-activated, the iridium photocatalyst attacks nicotinamide adenine dinucleotide (NADH), a vital co-enzyme that generates energy in cells. Cancer cells have a high requirement for NADH, as they need a lot of energy to rapidly divide and multiply. The activated iridium catalytically destroys NADH or changes it into its oxidized form, cutting off the tumour’s source of energy, even under hypoxia.
The researchers investigated the activity of the iridium compound on a range of cancer cell lines, as well as normal human cells. Upon light irradiation, they observed almost equivalent photocytotoxicity under normal levels of oxygen and under hypoxia. Unirradiated normal cells experienced low toxicity from the compound. They also studied a solid tumour model – lung cancer spheroids of roughly 800 µm diameter – and saw promising phototherapeutic effects.
“Now we have a potential new drug that 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 from Sun Yat-Sen University.
The selective targeting of PDT will also help reduce side effects of cancer treatment. “The compound that we have developed would not be very toxic at all,” explains Peter Sadler from the University of Warwick. 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.”
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The researchers also found that as the cancer cells died, they changed their chemistry in a way that generated an immune reaction in the body. This feature suggests that patients treated by this technique might be immunized against that cancer in the future.
“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,” explains Sadler. “It is very speculative, but we are looking further into the hallmarks of that.”
