Brain tumors are some of the hardest cancers to treat – unresponsive to treatment, difficult to access surgically, and quick to grow. Surgery, radiation, and chemotherapy drugs may all be enlisted to fight off a malignant glioma, but still the prognosis is often measured in months, according to Maciej Lesniak, associate professor of surgery and director of the Brain Tumor Center at the University of Chicago Medical Center. That creates a demand for inventive thinking about creative strategies to target tumor cells and extend the life of patients with brain cancer, Lesniak said.
“There have been advances in new therapies, but they haven’t been significant enough to make a tremendous difference in terms of extending the life of patients,” Lesniak said. “That puts you in a situation where due to the desperation, you start to look at novel, exciting and potentially interesting ways of developing new therapies for an incurable disease.”
Creative strategies such as really, really tiny magnetic golden pancakes.
Scientists from the Center for Nanoscale Materials and the Material Sciences Division at Argonne National Laboratory have been studying the “magnetic vortex state” of microdiscs – small iron-nickel discs so small that even “microscopic” over-characterizes their size – for several years. Applying even a weak magnetic field to these discs causes them to rotate, a property that Argonne’s Dong-Hyun Kim, Elena Rozhkova and Valentyn Novosad thought would be a possible weapon against cancer cells. If one could attach these discs to tumor cells, then expose them to a magnetic field to set them rotating, would their vibrations tear the cells apart?
That rather odd hypothesis was demonstrated to work in a recent paper published in the journal Nature Materials (News & Views article here), at least in the controlled environment of the test tube. Researchers coated the microdiscs in gold (to prevent rejection by the cells) and attached an antibody to target the discs to cancer cells but not normal cells. After giving the discs time to bind to cells, a very weak, alternating magnetic field – about the same strength as a magnetic screwdriver, Novosad said – was applied to the cells at a low frequency for 10 minutes.
The cells were not happy about this. When allowed to grow in culture after the magnetic field treatment, the cells were “rounded off, with membrane shrinkage and loss of membrane integrity” and “an apparent fractioning and redistribution of nucleus material.” In other words, they died. That was even more carnage than the researchers imagined, so much so that they had to reconfigure their hypothesis about how exactly the discs’ rotation would cause cell death.
“We didn’t expect much, when we tried the in vitro experiments,” Novosad said. “But the very first results were so surprising, the next experiments were just to confirm that we did indeed have such a strong anti-cancer effect.”
Rather than ripping holes in the membrane, further experiments found that the discs wreaked havoc through a more discrete mechanism. In the membrane of cells are a group of proteins called stretch receptors, portals that open when the skin of the cell is stretched. Once the doors are open, calcium flows into the cell – a good thing in small quantities, as calcium is responsible for neuronal communication and other functions. But when the stretch receptors are held open by rotating microdiscs, calcium floods into the cell and triggers apoptosis, also known by the intimidating name of “programmed cell death.” A refusal to undergo apoptosis is one hallmark of a tumor cell, so the oscillating microdiscs may disrupt tumors by convincing previously stubborn cells to die.
“Perhaps it doesn’t matter how it works. The important thing is that it works,” Lesniak said. “The great thing about this approach is it changes the mindset from trying to use pharmaceutical agents to do something to a cell to actually damaging the cancer cell in a mechanical fashion.”
The treatment, like the nanoscale photocatalysts I wrote about previously, is still many years away from clinical trials – Rozhkova, Novosad and Lesniak said that animal trials will begin shortly, with clinical trials to follow if results continue to be promising. Besides proving that the technique will work in an actual brain, the research must also make sure that the microdiscs do not have side effects that outweigh their benefit, either by killing off normal cells as well as tumor cells or producing an immune rejection by other parts of the body. How to get the microdiscs to the tumor is another problem to solve, Lesniak said; it’s possible that they could be merely injected into the blood, but it’s not clear whether they would reach the brain that way, or whether they would have to be directly applied to the tumor during surgery.
Regardless, it’s a promising technique, one that takes full advantage of a unique partnership between a leading research hospital and a leading materials research laboratory separated by only 25 miles of the Stevenson Expressway. And yet another potential use for nanomaterials, which Rozhkova likes to think of as the Swiss Army Knives of material science with applications for energy, manufacturing and medicine.
“For these magnetic particles, you cannot find any precedent in therapeutics or pharmaceutical agents because they are unique,” Rozhkova said. “These are excellent materials with lots of functions.”