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Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues
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Journal Article
Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues
2016
Overview
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.
The Food and Drug Administration (FDA)-approved iron supplement ferumoxytol, which contains iron oxide nanoparticles, can suppress growth of early mammary cancers and lung cancer metastasis by inducing pro-inflammatory M1 type macrophage polarization in the tumour tissue, offering a new ‘off label’ application for an approved drug.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antineoplastic Agents - chemistry
/ Antineoplastic Agents - pharmacology
/ Cancer
/ Cell Polarity - drug effects
/ Drugs
/ Female
/ Ferrosoferric Oxide - chemistry
/ Ferrosoferric Oxide - pharmacology
/ Humans
/ Iron
/ Liver
/ Liver Neoplasms - drug therapy
/ Lung Neoplasms - drug therapy
/ Mammary Neoplasms, Experimental - drug therapy
/ Mammary Neoplasms, Experimental - pathology
/ Metal Nanoparticles - chemistry
/ Metal Nanoparticles - therapeutic use
/ Nanotechnology and Microengineering
/ Tumors
