A team of researchers has been using the X-ray source PETRA III to visualise the spread of an anticancer drug in tumor cells
How can cancer drugs be delivered safely to their destination? An international team of researchers has been using the X-ray source PETRA III to test a technique for visualising how a drug is distributed inside tumor cells. In the future, this approach could help to develop more targeted and hence more effective cancer therapies. The working group has presented its findings in the journal Advanced Functional Materials.
Some anticancer drugs present a special challenge. They do not dissolve easily in the blood or they break down too quickly and because of this they are unable to reach the site where they are needed: the tumor. Researchers have come up with an ingenious strategy to overcome this: they enclose the drug in a molecular capsule. On being administered, this medication taxi makes its way through the body. Once it reaches the tumor, the capsule dissolves and releases the drug.
The only trouble is that it is difficult to observe how well this strategy is working. How do the drug capsules find their way into the tumor cells? And do they actually release the drug inside them? To answer these questions, researchers have until now had to label the drugs using special dyes. When a laser beam is shone at these, they light up like signal lamps and reveal the distribution of the drug inside a cell.
This method has its drawbacks, however. The markers are usually similar in size to the drug molecules themselves, and this can distort the readings. “It’s as if you were trying to track a fish through the ocean by fitting it with a transmitter that is as big as the creature itself,” explains Marvin Skiba, a PhD student in Wolfgang Parak’s group at the University of Hamburg’s Centre for Hybrid Nanostructures. “In that case, it’s doubtful whether the fish would move around in the same way as it would without the transmitter.” It would be helpful, therefore, to have a way of seeing the drug inside the medication taxi without having to label it with a dye.
One promising approach is X-ray fluorescence, a technique that can detect minute traces of a chemical element. The principle is straightforward. “When an X-ray beam strikes a sample, it excites the elements in it,” explains DESY physicist Gerald Falkenberg. “The excited atoms want to shed this energy quickly by emitting X-ray quanta. We use detectors to capture these quanta.”
The crucial point is that every element emits a different “X-ray colour”, thereby leaving its own distinctive fingerprint. The X-ray beam scans the sample line by line, creating a map of the elements. This requires a very powerful, narrow X-ray beam, such as the one generated by DESY’s X-ray source PETRA III at beamline P06.
To determine the suitability of this method for studying drugs transported in medication taxis, Skiba and Falkenberg’s team focused on a compound containing the element selenium, a potential therapeutic for treating tumors. “We enclosed the compound in a variety of different microparticles,” explains Marvin Skiba. “We then injected these into a cell culture and used X-rays to track how the selenium was distributed in the cells.”
Read more om DESY website
Image: Depending on the route of administration, the intracellular distribution of the selenium-based drug changes. When non-biodegradable polymers are used as the building blocks of the capsules, the selenium remains in the container and is not released (upper picture). The situation is different when amino acid and sugar-based vehicles are used which are digested by the cell and result in intracellular redistribution of the drug (lower picture). Cells are shown in grey while selenium is pseudocoloured from blue to yellow, depending on the concentration.
Credit: DESY, Marvin Skiba
