Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues

By Saeid Zanganeh, G. Hutter, R. Spitler, Olga D. Lenkov, M. Mahmoudi, Aubie Shaw, J. Pajarinen, Hossein Nejadnik, S. Goodman, Michael E. Moseley and 2 more. Nature Nanotechnology, 2016

1,440 citations recorded by the source corpus.

Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied ‘off label’ to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.

Subfields: Cancer Research, Immunology

View Paper: https://www.semanticscholar.org/paper/910dc261b9991b4310ac6fe5de1005a842014802

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In Cancer Research

1. Li Yang
2. S. Pun
3. Yi Zhang
4. Heather H Gustafson
5. T. Lammers
6. Chayanon Ngambenjawong

In Immunology

1. S. Pun
2. Heather H Gustafson
3. Chayanon Ngambenjawong

Citations in the corpus

• Iron Oxide Nanoparticles: Diagnostic, Therapeutic and Theranostic Applications (2019, background): “A key paper in this regard has been published by Zanganeh and colleagues, showing that the tumor growth inhibition caused by ferumoxytol is mediated by a shift in macrophage polarization towards a M1-like phenotype and to a concomitant increase in ROS production [213] (see Fig.”
• Progress in tumor-associated macrophage (TAM)-targeted therapeutics (2017, positive): “In light with the recent report on M1-inducing property of clinically approved iron oxide nanoparticles [145], it would be interesting to study how the iron oxide nanoparticle-loaded macrophages, already developed for diagnostic purpose, may exhibit enhanced anti-tumor properties.”
• Tumor-associated macrophages: from basic research to clinical application (2017, background): “found that ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice, and this tumor growth inhibition was accompanied by an increase in proinflammatory M1 macrophages in tumor tissues [70].”