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Using Diamond’s Hard X-ray Nanoprobe beamline (I14), researchers could see how Osmium, a rare precious metal that could be used for cancer treatments, reacts in a single human lung cancer cell. Dr Elizabeth Bolitho, from the University of Warwick, is the first joint PhD student with I14 and lead author on the research recently published in Angewante Chemie. The study is a major step forward in discovering new anti-cancer drugs, as currently half of the drugs used in chemotherapy contain the metal platinum. Once platinum is inside the cancer cell it reacts in the nucleus, which may lead to undesirable side effects of the treatment. However, as Osmium has fewer side effects it could be used as a new cancer treatment.
Elizabeth and the team used the 185 m I14 beamline to track Osmium in a single cancer cell at a scale of 100 nanometers for the first time. Elizabeth commented on the role of the beamline in her studies. She said:
I14 has been crucial for my research, as I have investigated a series of Osmium, iridium and platinum anticancer complexes in a variety of human cancer cell lines (including prostate, ovarian and lung cancers). This provides hope that in the future Osmium could be used to treat a range of different cancers.
We worked 24 hours a day, five days a week to collect these exciting data, allowing us to see inside cancer cells to a nanoscale resolution. This has provided crucial insights into potential cellular targets of such Osmium catalysts.
I have been involved in at least eight experiments at the I14 beamline, and it has become of significant importance for studying the biological activity of precious metal anticancer complexes.
The researchers used two techniques to track potential treatments in cancer cells. The first, ICP-MS (Inductively Coupled Plasma-Mass Spectrometry), can quantify a wide range of natural and drug elements in millions of cells. However, to investigate a single cancer cell, researchers used the synchrotron’s X-ray Fluorescence (XRF) imaging.
Professor Peter Sadler, from the Department of Chemistry at the University of Warwick, said:
With one in two people getting cancer in their lifetime, the need to find new drugs has never been more urgent. Part of drug discovery is seeing exactly how they react and work in cells.
Osmium is a rare precious metal, however, since it can act as a catalyst, a very little amount is needed for reactions in the cancer cell, therefore it could be a sustainable treatment going forward. We wanted to see how exactly it worked in a single cancer cell, which involved a variety of novel techniques, including taking water molecules out of the cell and rapidly flash-freezing it. Whereas usually cells are chemically altered to see the reactions, in our method they are close to their natural state, making our results more authentic.
Using the I14 beamline, researchers observed how Osmium reacted in a single lung cancer cell. However, the reactivity of Osmium is determined by its coating (its ligands), so they monitored the ligands too in the same XRF experiment by labelling them with Bromine. Once the Osmium was in the cell researchers observed that Osmium stays in the cytoplasm, whereas the ligands entered the nucleus, potentially indicative of dual attack on the cancer cell.
Prof. Sadler added: “Our team hopes to progress their discoveries through pre-clinical development towards new Osmium drugs for cancer treatment, although this typically takes several years. If we succeed, then the days and sleepless nights spent collecting XRF data at the Diamond synchrotron will certainly have been worthwhile.”
Paul Quinn, Imaging Group Leader at Diamond, commented:
The collaboration between Warwick and the I14 beamline is very exciting. Our research has exploited the advanced nano-imaging methods we’ve developed and built at Diamond to neatly image the location of these drugs within cancer cells and gain significant insights into how they interact.
Elizabeth concluded by noting how beneficial it has been to be working on I14 as the first PhD. She said:
“Throughout my PhD I was also fortunate enough to have first-hand experience into the new techniques and advances now available at the beamline, including differential phase contrast imaging, ptychography and XANES, with a resolution which can now reach down to 50 nm, and I am extremely excited about future collaborative publications with this beamline.
"Being a PhD student at Diamond is amazing, because I am able to collaborate with beamline scientists on a regular basis, and use state-of-the-art facilities to significantly advance the research, as well as contributing to such an exciting field.”
For more information about I14 at Diamond, or to discuss potential applications, please contact I14’s Principal Beamline Scientist, Paul Quinn: email@example.com
As a major UK science facility, Diamond offers exciting prospects for PhD students across a wide variety of scientific and technical areas. Find out more about Diamond’s PhD programme.
Elizabeth M. Bolitho et al. Tracking Reactions of Asymmetric Organo‐Osmium Transfer Hydrogenation Catalysts in Cancer Cells. Angewandte Chemie. DOI: 10.1002/anie.202016456
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