Ferumoxytol is an FDA-approved therapeutic for the treatment of anemia. It’s a solution of iron oxide nanoparticles roughly 17-31 nm in diameter and replenishes the body’s iron levels. Researchers from Stanford University have discovered a new use for these nanoparticles in that they may actually be protective against metastatic cancer spreading to the liver. When the investigators injected the nanoparticles into mice, and then challenged the mice with injections of cancer cells, they found a much lower tumor burden in the liver compared to mice that didn’t get any nanoparticles.
Publishing in Nature Nanotechnology, the authors attribute the effects to tumor-associated macrophages (TAMs), which are a type of immune system cell that lodge themselves among the nests of cancer cells and produce signals to help the cancer grow. Although delivery of targeted nanoparticles to cancer cells has been the overarching goal of cancer nanomedicine, TAMs seem to be a major roadblock and sequester much of the delivery inside the tumor. However, given the major role these TAMs play in the growth of tumors, recently they’ve become the subject of study as an alternative therapeutic target. The authors found that TAMs adopted a more anticancer phenotype after treatment with nanoparticles, compared to TAMs in mice without particles. Interestingly, the authors chose to deliver the nanoparticles with the injection of cancer cells during tumor induction (this would never be the case in humans, and so the relevance is unclear). In vitro mechanistic studies showed that TAMs released oxidation products that caused nearby cancer cells to self-destruct.
Now, is this just another study that promises to cure cancer? It’s hard to say whether or not this will work; plenty of papers are published daily that report on “shrinking tumours” with a new nanoparticle. However, it’s a refreshing take on an old idea – to instead study the nanoparticle interactions with the non-cancer cells of a tumor. There’s increasing evidence now that cancer drugs work in part by stimulating the immune system to attack the cancer, and this study adds additional power to that claim. The authors could have strengthened their conclusions with more direct evidence that nanoparticles modify TAMs and induce cancer cell auto-destruction in an actual mouse, rather than only in Petri dish cells. Furthermore, the authors did not study liver toxicity, and only cited other works that showed nontoxicity with iron oxide particles. They concluded by suggesting to perform a retrospective clinical study comparing liver metastatic burdens in cancer patients who have received ferumoxytol versus patients who have not. Seems like a sensible and cost-effective proposal that could draw relevance to humans for a potential “off-label” anti-metastatic drug.
Study in Nature Nanotechnology: Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues…