title: Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro.
abstract: Ferumoxtran-10, a dextran-coated ultrasmall superparamagnetic iron oxide particle, has the potential to reveal macrophages in vivo using magnetic resonance imaging potentially acting as a marker of inflammatory status. Pending clinical trials, we examined the interactions of Ferumoxtran-10 with human monocyte-macrophages (HMMs) in vitro to assess its safety and lack of pro-inflammatory activity. After 72 h, Ferumoxtran-10 was not toxic at 1 mg/ml and may be only mildly toxic at 10 mg/ml. Viability in cells with a high intracellular Ferumoxtran-10 load was not affected over 14 days. Ferumoxtran-10 did not interfere with baseline or stimulated cytokine (interleukin-12, interleukin-6, tumour necrosis factor-alpha or interleukin-1beta) or superoxide anion production or with Fc-receptor-mediated phagocytosis. Similarly, Ferumoxtran-10 did not induce cytokine production and was not chemotactic. High-resolution electron microscopy and selected-area electron diffraction confirmed the core of Ferumoxtran-10 is composed of crystalline magnetite. Bright field transmission electron microscopy of thin sections demonstrated that Ferumoxtran-10 was retained in lysosomes of HMM for several days. Ferumoxtran-10 is not toxic to HMMs in vitro, does not activate them to produce pro-inflammatory cytokines or superoxide anions, is not chemotactic and does not interfere with Fc-receptor-mediated phagocytosis. Furthermore, extremely high intracellular Ferumoxtran-10 concentrations had only slight or no effects on these key activities.
authors.affiliation: Multi-Imaging Centre, Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. khm20@hermes.cam.ac.uk
authors.forename: Karin
authors.initials: K
authors.lastname: Müller
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Skepper
authors.forename: Mihaly
authors.initials: M
authors.lastname: Posfai
authors.forename: Rikin
authors.initials: R
authors.lastname: Trivedi
authors.forename: Simon
authors.initials: S
authors.lastname: Howarth
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
authors.forename: Eric
authors.initials: E
authors.lastname: Lancelot
authors.forename: Paul W
authors.initials: PW
authors.lastname: Thompson
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Brown
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gillard
mesh_terms: D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects / Q000493:pharmacokinetics; D016207:Cytokines / Q000276:immunology; D003911:Dextrans; D004305:Dose-Response Relationship, Drug; D052203:Ferrosoferric Oxide; D006801:Humans; D007501:Iron / Q000009:adverse effects* / Q000493:pharmacokinetics; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D058185:Magnetite Nanoparticles; D008422:Materials Testing; D049329:Nanostructures / Q000009:adverse effects / Q000648:ultrastructure; D010087:Oxides / Q000009:adverse effects* / Q000493:pharmacokinetics; D010316:Particle Size
chemical_list: D003287:Contrast Media; D016207:Cytokines; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D052203:Ferrosoferric Oxide