Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro

Karin Müller, Jeremy N. Skepper, Mihaly Posfai, Rikin Trivedi, Simon Howarth, Claire Corot, Eric Lancelot, Paul W. Thompson, Andrew P. Brown, Jonathan H. Gillard

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186 Citations (Scopus)

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-α or interleukin-1β) 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.

Original languageEnglish
Pages (from-to)1629-1642
Number of pages14
JournalBiomaterials
Volume28
Issue number9
DOIs
Publication statusPublished - Mar 1 2007

Keywords

  • Cell activation
  • Cytotoxicity
  • Electron microscopy
  • Inflammation
  • Macrophage
  • Nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Müller, K., Skepper, J. N., Posfai, M., Trivedi, R., Howarth, S., Corot, C., Lancelot, E., Thompson, P. W., Brown, A. P., & Gillard, J. H. (2007). Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro. Biomaterials, 28(9), 1629-1642. https://doi.org/10.1016/j.biomaterials.2006.12.003