Mechanism of Iron Oxide-Induced Macrophage Activation: The Impact of Composition and the Underlying Signaling Pathway.
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Peer-reviewed
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Abstract
Iron oxide nanoparticles (IONPs) have emerging anticancer applications via polarizing tumor-associated macrophages from tumor-promoting phenotype (M2) to tumor-suppressing phenotype (M1). However, the underlying mechanism and structure-function relationship remain unclear. We report magnetite IONPs are more effective compared to hematite in M1 polarization and tumor suppression. Moreover, magnetite IONPs specifically rely on interferon regulatory factor 5 signaling pathway for M1 polarization and down-regulate M2-assoicated arginase-1. This study provides new understandings and paves the way for designing advanced iron-based anticancer technologies.
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Keywords
Animals, Ferric Compounds, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Nanoparticles, Phenotype, RAW 264.7 Cells, Signal Transduction
Journal Title
J Am Chem Soc
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0002-7863
1520-5126
1520-5126
Volume Title
141
Publisher
American Chemical Society (ACS)
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All rights reserved
Sponsorship
The authors acknowledge the support from the Australian Research Council, Australian Microscopy and Microanalysis Research Facil- ity at the Centre for Microscopy and Microanalysis and the Aus- tralian National Fabrication Facility at the University of Queens- land. Z.Y.G acknowledges the Australia Research Training Pro- gram (RTP) Scholarship. Z.K.T. is supported by an Advance Queensland Research Fellowship.