Superparamagnetic iron oxide nanoparticle uptake alters M2 macrophage phenotype, iron metabolism, migration and invasion

• Published in: Nanomedicine Vol. 12; no. 4; pp. 1127 - 1138
• Main Authors: Rojas, José M, Sanz-Ortega, Laura, Mulens-Arias, Vladimir, Gutiérrez, Lucía, Pérez-Yagüe, Sonia, Barber, Domingo F
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2016
• Subjects: Animals; Cell Differentiation - drug effects; Cell Movement - drug effects; Contrast Media - administration & dosage; Contrast Media - adverse effects; Ferric Compounds - administration & dosage; Ferric Compounds - adverse effects; Humans; IL-10; Internal Medicine; Iron - metabolism; M2 macrophage; Macrophage invasion; Macrophages - drug effects; Magnetic Resonance Imaging; Magnetite Nanoparticles - administration & dosage; Magnetite Nanoparticles - adverse effects; Mice; Neoplasm Invasiveness - diagnostic imaging; Neoplasms - diagnostic imaging; Neoplasms - pathology; Reactive Oxygen Species - metabolism; SPION; APS; JNK; 3-aminopropyl-triethoxysilane; TFR/TfR; PFA; TNF; MPS; Polyethylenimine; Iron response element; Th; FPN-1; Lipopolysaccharide; Bone marrow-derived macrophages; RT-qPCR; T helper; Toll-like receptor; c-Jun N-terminal kinase; AD; IL; Divalent metal transporter-1; MAPK; DMT-1; Superparamagnetic iron oxide nanoparticles; IL-10; MMP; TGF; DMSA; ROS; Real-time quantitative polymerase chain reaction; IRE; ERK; Paraformaldehyde; Iron-responsive element-binding proteins; Reactive oxygen species; Iron metabolism; Interleukin; IRP; Tumour growth factor; LPS; BMM-M2; IFN; MFI; Tumour necrosis factor; Aminodextran; Metalloproteinase; TLR; SPION; BMM; PMA; Mean fluorescence intensity; Extracellular signal-regulated kinase; Mitogen-activated protein kinase; Transferrin receptor; Ferroportin-1; Dimercaptosuccinic acid; M2 macrophage; Macrophage invasion; PEI; Interferon; Mononuclear phagocyte system; Phorbol 12-myristate 13-acetate; Bone marrow-derived macrophages polarised to M2
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2015.11.020

Abstract Superparamagnetic iron oxide nanoparticles (SPIONs) have shown promise as contrast agents and nanocarriers for drug delivery. Their impact on M2-polarised macrophages has nonetheless not been well studied. Here we explored the effects of SPIONs coated with dimercaptosuccinic acid, aminopropyl silane or aminodextran in two M2 macrophage models (murine primary IL-4-activated bone marrow-derived macrophages and human M2-like differentiated THP-1 cells). All SPIONs were internalised and no cell toxicity was observed. SPION treatment produced reactive oxygen species and activated the extracellular signal-regulated kinase and AKT pathways. After 24-h SPION incubation, M2 macrophages switched their iron metabolism towards an iron-replete state. SPION treatment in both M2 macrophage models altered their M2 activation profiles, promoted IL-10 production, and stimulated protease-dependent invasion. These results highlight the need to evaluate the interactions between SPIONs and cells to take full advantage of the intrinsic properties of these nanoparticles in biological systems.