A team of researchers from the University of Warwick in the UK and Sun-Yat Sen University in China has discovered that cancer cells can be killed with a compound based on iridium from the asteroid that is hypothesized to have caused the extinction of the dinosaurs.
“We found that the asteroid metal iridium can absorb light strongly and become phosphorescent after we coat it with certain organic ligands,” explains Professor Peter Sadler from Warwick’s Department of Chemistry. “Then, on illumination with light, the organo-iridium compound can transfer energy to normal oxygen that we breathe and convert it into highly reactive, destructive singlet oxygen.”
Sadler and his colleagues administered this compound of organic material and iridium (after osmium the second densest metal found on earth) to cancer cells, where it generated singlet oxygen when activated by visible laser light, which then destroyed the cancer cells, without harming healthy tissue.
The process of destroying the cancer cells
“Upon irradiation, the drug converts ordinary ‘triplet’ oxygen to toxic ‘singlet’ oxygen, introducing oxidative stress in cells and disrupting their micro-environment, which eventually kills them,” Sadler says.
The international team has also for the first time ascertained what parts of cancer cells are affected by treatment. Sadler reports that data from the mass spectrometry study shows specific attack on important proteins in the glycolytic pathway, specifically around the mitochondria, where energy is generated in cells, disrupting their energy supply.
“The biggest surprise of this research is that we discovered specific attack on two important cellular proteins in cancer cells whereas it might have been thought that singlet oxygen would damage most cellular proteins indiscriminately,” Sadler says. “Such an effect has not been reported before.”
The role of mass spectrometry in the study
“We used ultrahigh-resolution Fourier transform mass spectrometry (MS) to ‘weigh’ a very large number of proteins in cancer cells very precisely to locate the amino acids on them which had been altered by singlet oxygen attack,” says Sadler, adding that mass spectrometry also revealed important effects on the pathways in which glucose is metabolized and energy generated in cancer cells.
The researchers credit significant advances in modern mass spectrometry for their ability to now analyze complex mixtures of proteins in cancer cells and pinpoint drug targets, on instruments that are sensitive enough to weigh even a single electron.
Impact on future cancer research and treatment
“We are trying to rise to the challenge of designing cancer treatments which cause less harm to normal tissues, less side effects, and can attack cancer cells in completely new ways, so combating resistance. Resistance is life-threatening in cancer treatment. Our discovery of organo-iridium compounds which can cause selective damage to cancer cells over normal cells and attack specific biochemical pathways offers a new way forward, although there is still much preclinical development to be done before patients can be treated.”
Advance photochemotherapy as cancer treatment
The professor believes that the use of near infrared light — two photon laser light — could significantly enhance tissue penetration depth into tumors. “It is very precise and could pinpoint attack on cancer cells and spare normal cells,” he says, adding that he and his colleagues hope that advances in the technology of two-photon production and use “might make this a practical possibility in future.”
Going forward, the international collaborators are planning to study a wide range of cancer models and investigate how this new technology could progress towards clinical trials. “This UK-China cooperation has been very successful so far and we hope it will hasten the approach towards the clinic in future,” concludes Sadler.
The paper “Organo-iridium photosensitizers can induce specific oxidative attack on proteins in cancer cells” is published in Angewandte Chemie.
Written by Sandra Henderson, Research Editor, Novus Light Technologies Today