An international group of scientists has demonstrated that iridium — a very hard, silvery-white transition metal of the platinum group — can be used to kill cancer cells by filling them with deadly version of oxygen, without harming healthy tissue. The study is published in the journal Angewandte Chemie.
“The precious metal platinum is already used in more than 50% of cancer chemotherapies,” said lead co-author Professor Peter Sadler, from the University of Warwick, UK.
“The potential of other precious metals such as iridium to provide new targeted drugs which attack cancer cells in completely new ways and combat resistance, and which can be used safely with the minimum of side-effects, is now being explored.”
“Our project is a leap forward in understanding how these new iridium-based anti-cancer compounds are attacking cancer cells, introducing different mechanisms of action, to get around the resistance issue and tackle cancer from a different angle,” said co-author Dr. Cookson Chiu, a postgraduate researcher at the University of Warwick.
“Our innovative approach to tackle cancer involving targeting important cellular proteins can lead to novel drugs with new mechanisms of action. These are urgently needed,” said first author Dr. Pingyu Zhang, from the University of Warwick and Shenzhen University in China.
The researchers created a compound of iridium and organic material, which can be directly targeted towards cancerous cells, transferring energy to the cells to turn the oxygen inside them into singlet oxygen, which is poisonous and kills the cell — without harming any healthy tissue.
The process is triggered by shining visible laser light through the skin onto the cancerous area — this reaches the light-reactive coating of the compound, and activates the metal to start filling the cancer with singlet oxygen.
They found that after attacking a model tumor of lung cancer cells, grown in the lab to form a tumor-like sphere, with red laser light (which can penetrate deeply through the skin), the activated organic-iridium compound had penetrated and infused into every layer of the tumor to kill it — demonstrating how effective and far-reaching this treatment is.
They also proved that the method is safe to healthy cells by conducting the treatment on non-cancerous tissue and finding it had no effect.
Furthermore, the team used state-of-the-art ultra-high resolution mass spectrometry to gain an unprecedented view of the individual proteins within the cancer cells — allowing them to determine precisely which proteins are attacked by the organic-iridium compound.
After vigorously analyzing huge amounts of data — thousands of proteins from the model cancer cells, they concluded that the iridium compound had damaged the proteins for heat shock stress, and glucose metabolism, both known as key molecules in cancer.
“Remarkable advances in modern mass spectrometry now allow us to analyze complex mixtures of proteins in cancer cells and pinpoint drug targets, on instruments that are sensitive enough to weigh even a single electron,” said lead co-author Professor Peter O’Connor, also from the University of Warwick.
Pingyu Zhang et al. Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells. Angewandte Chemie, published online October 19, 2017; doi: 10.1002/anie.201709082