title: Superparamagnetic iron oxide nanoparticle uptake alters M2 macrophage phenotype, iron metabolism, migration and invasion.
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.
  
  
  BACKGROUND
  Superparamagnetic iron oxide nanoparticles (SPIONs) have been used as an MRI contrast agent in many experimental studies. The authors here investigated the effects of these nanoparticles on M2 macrophages after cellular uptake. The findings of cell activation further enhanced our current knowledge on the interaction of SPIONS with macrophages.
authors.affiliation: Department of Immunology and Oncology and Nanobiomedicine Initiative, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas (CNB-CSIC), Madrid, Spain. Electronic address: jmrojas@cnb.csic.es.
authors.forename: José M
authors.initials: JM
authors.lastname: Rojas
authors.affiliation: Department of Immunology and Oncology and Nanobiomedicine Initiative, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas (CNB-CSIC), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanz-Ortega
authors.affiliation: Department of Immunology and Oncology and Nanobiomedicine Initiative, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas (CNB-CSIC), Madrid, Spain.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mulens-Arias
authors.affiliation: Department of Biomaterials and Bioinspired Materials, Instituto de Ciencias Materiales de Madrid/CSIC (ICMM-CSIC), Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Gutiérrez
authors.affiliation: Department of Immunology and Oncology and Nanobiomedicine Initiative, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas (CNB-CSIC), Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Pérez-Yagüe
authors.affiliation: Department of Immunology and Oncology and Nanobiomedicine Initiative, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas (CNB-CSIC), Madrid, Spain. Electronic address: dfbarber@cnb.csic.es.
authors.forename: Domingo F
authors.initials: DF
authors.lastname: Barber
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007501:Iron / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000000981:diagnostic imaging; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C000499:ferric oxide; D007501:Iron
keywords: IL-10; Iron metabolism; M2 macrophage; Macrophage invasion; SPION