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Old technique gives new insight into killing cancer cells

At the centre of an exciting advance in cancer treatment is a pioneering platinum-based chemotherapy drug candidate called trans,trans,trans-[Pt(N3)2(OH)2(py)2]. The drug is an inorganic-metal compound, originally developed by Professor Peter Sadler’s research group at the University of Warwick, and has been given a new lease of life by a Monash Warwick Alliance team led by PhD student Robbin Vernooij. The team observed what happened to the structure of the compound when it was irradiated by light, and found that it has an unusual mechanism that can kill cancerous cells in targeted areas, minimising toxic side effects on healthy tissue – an incredible development for the field.

This drug is a photoactivatable platinum diazido complex, meaning it’s a platinum compound which is completely inactive and non-toxic in the dark, and is activated by light. Platinum is a transition metal, these metals create complexes that offer a large ‘scope for selective interference’ in biological pathways, and so have great potential for use in therapeutics, with ‘novel modes of action’ and unusual properties, as stated in Professor Sadler’s group’s 2012 paper in Molecular Cancer Therapeutics. The treatment can then be inserted into cancerous areas and its functions are only triggered when hit by directed light. Once this happens, the compound degrades into active platinum, releasing ligand molecules to attack cancerous cells. Vernooij stated that these developments could bring scientists “closer to our goal of making more selective and effective cancer treatments.”

The treatment can then be inserted into cancerous areas and its functions are only triggered when hit by directed light

In the study, published this month in Chemistry: A European Journal, the researchers discovered the compound’s properties using an old technique, infrared spectroscopy, shining infrared light on the drug and measuring the vibrations of the molecules which were subsequently released as it was activated. This gave them information on the chemical and physical properties of the compound. Some of the ligands attached to the platinum metal become detached and are replaced with water, whilst other ligands remain stable around the metal. Professor Sadler believes these platinum compounds can “attack cancerous cells in totally new ways can combat resistance”, a growing issue in cancer treatment. The discoveries give new insights into the underlying mechanisms of platinum-based drugs, and new hope for its future testing in clinical trials and a new age of cancer treatment.

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