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

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

Research output: Contribution to journalArticle

179 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 2007

Fingerprint

Macrophages
Iron oxides
Nanoparticles
Monocytes
Negative ions
Poisons
Dextran
High resolution electron microscopy
Magnetite
Magnetic resonance
Electron diffraction
Fc Receptors
Cytokines
Phagocytosis
Superoxides
Crystalline materials
Transmission electron microscopy
Imaging techniques
In Vitro Techniques
ferumoxtran-10

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro. / Müller, Karin; Skepper, Jeremy N.; Pósfai, M.; Trivedi, Rikin; Howarth, Simon; Corot, Claire; Lancelot, Eric; Thompson, Paul W.; Brown, Andrew P.; Gillard, Jonathan H.

In: Biomaterials, Vol. 28, No. 9, 03.2007, p. 1629-1642.

Research output: Contribution to journalArticle

Müller, K, Skepper, JN, Pósfai, M, Trivedi, R, Howarth, S, Corot, C, Lancelot, E, Thompson, PW, Brown, AP & Gillard, JH 2007, 'Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro', Biomaterials, vol. 28, no. 9, pp. 1629-1642. https://doi.org/10.1016/j.biomaterials.2006.12.003
Müller, Karin ; Skepper, Jeremy N. ; Pósfai, M. ; Trivedi, Rikin ; Howarth, Simon ; Corot, Claire ; Lancelot, Eric ; Thompson, Paul W. ; Brown, Andrew P. ; Gillard, Jonathan H. / Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro. In: Biomaterials. 2007 ; Vol. 28, No. 9. pp. 1629-1642.
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