Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific

Heather L. McConnell, Daniel L. Schwartz, Brian E. Richardson, Randall (Randy) Woltjer, Leslie Muldoon, Edward Neuwelt

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Ferumoxytol ultrasmall superparamagnetic iron oxide nanoparticles can enhance contrast between neuroinflamed and normal-appearing brain tissue when used as a contrast agent for high-sensitivity magnetic resonance imaging (MRI). Here we used an anti-dextran antibody (Dx1) that binds the nanoparticle's carboxymethyldextran coating to differentiate ferumoxytol from endogenous iron and localize it unequivocally in brain tissue. Intravenous injection of ferumoxytol into immune-competent rats that harbored human tumor xenograft-induced inflammatory brain lesions resulted in heterogeneous and lesion-specific signal enhancement on MRI scans in vivo. We used Dx1 immunolocalization and electron microscopy to identify ferumoxytol in affected tissue post-MRI. We found that ferumoxytol nanoparticles were taken up by astrocyte endfeet surrounding cerebral vessels, astrocyte processes, and CD163+/CD68+ macrophages, but not by tumor cells. These results provide a biological basis for the delayed imaging changes seen with ferumoxytol and indicate that ferumoxytol-MRI can be used to assess the inflammatory component of brain lesions in the clinic.

Original languageEnglish (US)
Pages (from-to)1535-1542
Number of pages8
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume12
Issue number6
DOIs
StatePublished - Aug 1 2016

Keywords

  • Contrast agents
  • Iron oxide nanoparticles
  • Macrophages
  • MRI
  • Neuroinflammation

ASJC Scopus subject areas

  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Medicine (miscellaneous)
  • Pharmaceutical Science

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