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

13 Citations (Scopus)

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

Fingerprint

Ferrosoferric Oxide
Nanoparticles
Magnetic resonance
Brain
Imaging techniques
Magnetic Resonance Imaging
Tissue
Tumors
Astrocytes
Dextran
Macrophages
Iron oxides
Antibodies
Electron microscopy
Rats
Cells
Dextrans
Heterografts
Iron
Intravenous Injections

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

Cite this

Ferumoxytol nanoparticle uptake in brain during acute neuroinflammation is cell-specific. / McConnell, Heather L.; Schwartz, Daniel L.; Richardson, Brian E.; Woltjer, Randall (Randy); Muldoon, Leslie; Neuwelt, Edward.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 12, No. 6, 01.08.2016, p. 1535-1542.

Research output: Contribution to journalArticle

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