Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues.
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.
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, 725 Welch Road, Stanford, California 94305, USA.|Institute of Stem Cell Research and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Saeid
S
Zanganeh
Institute of Stem Cell Research and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.|Department of Neurosurgery, Stanford University, Stanford, California 94305, USA.
Gregor
G
Hutter
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, 725 Welch Road, Stanford, California 94305, USA.
Ryan
R
Spitler
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, 725 Welch Road, Stanford, California 94305, USA.|Institute of Stem Cell Research and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Olga
O
Lenkov
Department of Medicine, Division of Cardiology, Stanford University, Stanford, California 94305, USA.
Morteza
M
Mahmoudi
Department of Cell, Developmental &Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
Aubie
A
Shaw
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University, Stanford, California 94305, USA.
Jukka Sakari
JS
Pajarinen
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, 725 Welch Road, Stanford, California 94305, USA.|Institute of Stem Cell Research and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.
Hossein
H
Nejadnik
Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, Stanford University, Stanford, California 94305, USA.
Stuart
S
Goodman
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, 725 Welch Road, Stanford, California 94305, USA.
Michael
M
Moseley
Department of Cell, Developmental &Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.
Lisa Marie
LM
Coussens
Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, 725 Welch Road, Stanford, California 94305, USA.|Institute of Stem Cell Research and Regenerative Medicine, Stanford University, Stanford, California 94305, USA.|Department of Pediatrics, Stanford University, Stanford, California 94305, USA.
Heike Elisabeth
HE
Daldrup-Link
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016764:Cell Polarity / Q000187:drug effects; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008264:Macrophages / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D052203:Ferrosoferric Oxide
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