Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues
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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.
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The other study suggested that IONs stimulate TNF expression while inhibiting arginase-1 which results in improved killing of tumor cells.
“The other study suggested that IONs stimulate TNF expression while inhibiting arginase-1 which results in improved killing of tumor cells [257].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [257]
Application of nanoparticles to tumor-bearing mice is sufficient to induce clinical remission.
“Two elegant studies have shown that the application of nanoparticles to tumor-bearing mice is sufficient to induce clinical remission.”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [257]
Tumor growth inhibition caused by ferumoxytol is mediated by a shift in macrophage polarization toward M1-like phenotype and increased ROS production.
“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 [214] (see Figure 6 B-C).”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [214]
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- Authors
- Zanganeh, S., Hutter, G., Spitler, R., Lenkov, O., Mahmoudi, M., Shaw, A., Pajarinen, J. S., Nejadnik, H., Goodman, S., Moseley, M., Coussens, L. M., & Daldrup-Link, H. E.
- Affiliations
- Stanford Medicine (US)
- Oregon Health & Science University (US)
- Corresponding author
- Daldrup-Link, Heike Elisabeth
- ORCID
- Venue
- Nature Nanotechnology
- Published
- 2016-09-26
- Volume
- 11
- Issue
- 11
- Pages
- 986-994
- ISSN
- 1748-3387 (ISSN-L)
- 1748-3395
- PMC
- PMC5198777
- OpenAlex
- W2427645657
- Cited by
- 1,647
- References
- 52
- Citations by year
- 2026: 103 · 2025: 147 · 2024: 192 · 2023: 195 · 2022: 225 · 2021: 216 · 2020: 208 · 2019: 178 · 2018: 102 · 2017: 76 · 2016: 3 · 2014: 1
- FWCI
- 72.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (155336)
- National Institutes of Health
- National Cancer Institute (P50CA114747, R21CA176519, R21CA190196, R21CA156124, Z01BC010412, P30CA124435, T32CA009695)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- ferumoxytol, iron oxide nanoparticles, tumor growth inhibition, M1 macrophage polarization, inflammatory macrophages, mammary adenocarcinoma, lung cancer metastasis, liver metastasis, Th1 response, caspase-3, cancer immunotherapy
- MeSH terms
- Animals, Antineoplastic Agents, Female, Humans, Inflammation, Liver Neoplasms, Lung Neoplasms, Macrophages, Mammary Neoplasms, Experimental, Mice, Inbred Strains, Mice, Inbred NOD, Cell Polarity, Xenograft Model Antitumor Assays, Cell Line, Tumor, Ferrosoferric Oxide, Metal Nanoparticles
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