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Iron Nanoparticles Trigger Immune System Offensive Against Cancer

An accidental discovery offers new immunotherapy hope.
Macrophages in action. Image: sciencepics/Shutterstock

The paradox of cancer, what makes it so insidious, is that it is us. Bacteria, viruses, and fungi represent invaders—their DNA is that of another organism (or virus). Our immune systems recognize these things as such, and they respond defensively. In most cases these responses are successful. Cancer, however, elicits little such defense because it's just another part of our bodies. Cancerous cells may be brash, immature, and ultimately deadly, but it's an internal revolt. The immune system steps aside.


A great hope of cancer researchers is in harnessing the immune system as an anti-cancer force. This is broadly known as immunotherapy, or, in some cases, biological therapy. Immunotherapy is becoming more and more common in cancer treatment, but it's still a limited approach, effective for only some cancers and usually in concert with more traditional cancer therapies (chemo, radiation, surgery).

Recently, researchers from Stanford University discovered quite by accident that regular old iron nanoparticles, in the form of the injectable supplement ferumoxytol (currently used to treat iron-deficiency anemia), have a potent immune system rallying effect in mice. Simply, ferumoxytol prompts immune cells called macrophages to attack and destroy tumor cells. It seems likely the concept could extend to human patients, according to a study published Monday in Nature Nanotechnology.

The Stanford group's original idea was that iron nanoparticles could be used as "Trojan horses" for sneaking chemotherapy drugs into tumors, thus increasing their anticancer efficacy. To test this, they conducted an experiment in which chemotherapy drugs bound to iron nanoparticles were delivered to tumors. The experiment also included two control groups: One group received only the nanoparticles, while the second received nothing at all. Compared to the second control, the nanoparticle-only group showed a significant decrease in tumor growth rate.


This was unexpected.

"Our data show that ferumoxytol nanoparticles rather cause tumour growth inhibition through indirect effects on the tumour microenvironment," the paper explains.

Macrophages, which basically operate by swallowing certain bad things in their environment, are a natural built-in defense against cancer cells. The immune system isn't totally blind to the threat, after all. However, in the presence of large tumors, macrophages start having the opposite effect and instead secrete factors that promote tumor growth. By tweaking this environment via iron nanoparticles, the macrophages again start recognizing and attacking cancer cells.

This is a tricky thing. What's at work is the Fenton reaction, in which free radicals are produced and oxidative stress occurs against, among other things, DNA. So, iron can have the effect of supporting cancer via this reaction, but things can work the other way too. The Fenton reaction here induces cell apoptosis—programmed cell death—in tumors.

The Stanford researchers investigated this surprising effect further using three specific cancers. In mouse models of breast cancer, they found that, given iron doses on par with those approved by the FDA for treatment of anemia, tumors were significantly inhibited. To see if the nanoparticles had any effect on cancer metastasis—the process by which cancer spreads from tissue to tissue and from organ to organ—they treated mice with small-cell lung cancer in the hope that this would have an effect on the cancer's spread to the liver, a common metastatic outcome. Indeed, tumor formation in the liver was reduced. Finally, the group found that by pretreating mice with iron nanoparticles prior to the introduction of cancer cells, they could decrease the volume of the eventual liver tumors.

Part of what makes this exciting is that this is a treatment that's already on the market. As such, trials can expand quickly from mice to humans.

"These results have major implications for diagnostic and therapeutic applications of iron oxide nanoparticles," the paper concludes. "Because ferumoxytol is FDA-approved, our approach is immediately accessible for cancer patients through 'off label' use."