Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology

PLoS One. 2011;6(9):e25524. doi: 10.1371/journal.pone.0025524. Epub 2011 Sep 28.


Superparamagnetic iron oxide (SPIO) nanoparticles are contrast agents used for magnetic resonance imaging. Ferucarbotran is a clinically approved SPIO-coated carboxydextran with a diameter of about 45-60 nm. We investigated the mechanism of cellular uptake of Ferucarbotran with a cell model using the murine macrophage cell line Raw 264.7. We observed a dose-dependent uptake of these SPIO particles by spectrophotometer analysis and also a dose-dependent increase in the granularity of the macrophages as determined by flow cytometry. There was a linear correlation between the side scattering mean value and iron content (P<0.001, R(2) = 0. 8048). For evaluation of the endocytotic pathway of these ingested SPIO particles, different inhibitors of the endocytotic pathways were employed. There was a significant decrease of side scattering counts in the cells and a less significant change in signal intensity based on magnetic resonance in the phenylarsine oxide-treated macrophages. After labeling with SPIO particles, the macrophages showed an increase in the production of reactive oxygen species at 2, 24, and 48 h; a decrease in mitochondrial membrane potential at 24 h; and an increase in cell proliferation at 24 h. We concluded that Ferucarbotran was internalized into macrophages via the clathrin-mediated pathway and can change the cellular behavior of these cells after labeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival
  • Contrast Media / pharmacology
  • Dextrans / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Endocytosis
  • Flow Cytometry / methods
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Magnetite Nanoparticles / chemistry
  • Mice
  • Monocytes / cytology
  • Nanoparticles / chemistry
  • Reactive Oxygen Species
  • Scattering, Radiation
  • Spectrophotometry / methods
  • Time Factors


  • Contrast Media
  • Dextrans
  • Magnetite Nanoparticles
  • Reactive Oxygen Species
  • ferumoxides