Recently, a team of Stanford researchers was testing a new way to fight cancer when something strange happened.
The team, led by pediatric radiologist Heike Daldrup-Link, MD, was studying whether tiny bits of iron could act as Trojan horses, sneaking chemotherapy into tumor cells. There is growing evidence that attaching chemo to specially-engineered nanoparticles makes it easier to get drugs into malignant cells, exactly where they are needed. Daldrup-Link's team wondered if an FDA-approved anemia treatment made of iron nanoparticles could do this.
So they tested the idea using three groups of mice, all with malignant tumors. The experimental group got nanoparticles with chemo attached, while the two control groups received either nanoparticles only, or nothing at all. The researchers expected that the two control groups would fare worse than the mice getting chemotherapy.
"To our surprise, we saw that the growth of the tumors was much suppressed in the animals getting only nanoparticles compared with our other controls that were not treated at all," Daldrup-Link told me. Somehow, the nanoparticles could work against cancer without any chemotherapy present. "It was an unanticipated finding, an accident."
The team did a series of follow-up tests to figure out what was going on, and determined that the nanoparticles prompt a specific kind of immune cell, called tumor-associated macrophages, to attack cancer. Instead of Trojan horses, the bits of iron function more like master spies who can influence double agents (the immune cells) to change sides. Here are more details from our press release about the results, which were published this week in Nature Nanotechnology:
Before this study was done, it was already known that in healthy people, tumor-associated macrophages detect and eat individual tumor cells. However, large tumors can hijack the tumor-associated macrophages, causing them to stop attacking and instead begin secreting factors that promote the cancer’s growth.
The study showed that the iron nanoparticles switch the macrophages back to their cancer-attacking state, as evidenced by tracking the products of the macrophages’ metabolism and examining their patterns of gene expression.
'In many studies, researchers just consider nanoparticles as drug vehicles,' [Daldrup-Link] said. 'But they may have hidden intrinsic effects that we won’t appreciate unless we look at the nanoparticles themselves.'
Because the iron nanoparticles are already FDA approved, it should be fairly straightforward to test their possible anti-cancer activity in people. Daldrup-Link and her team have several ideas for how to do that, and they're excited to see where the work leads.
Previously: Trojan horses: Nanoparticles sneak drugs into brain to battle cancer, Dynamic duo: Nanoparticle/prodrug combination finds and fights tumors, files reports and Nanoparticles home in on human tumors growing in mice's brains, increase accuracy of surgical removal
Image by Emory Allen