Europium doping of superparamagnetic iron oxide nanoparticles enables their detection by fluorescence microscopy and for quantitative analytics

Technol Health Care. 2017;25(3):457-470. doi: 10.3233/THC-161285.


Background: Pharmacokinetic studies and histological detection of superparamagnetic iron oxide nanoparticles (SPIO) in biomedical research are limited due to a high iron background especially in pathological tissues.

Objective: The suitability of doping the iron oxide cores of SPIO with europium (Eu) was tested for improved histologic detection and for quantitative analysis without changing their properties as probes for magnetic resonance imaging (MRI). A special variant of SPIO, so called very small superparamagnetic iron oxide nanoparticles (VSOP), was used for this approach.

Methods: VSOP, stabilized by a citrate coating, were synthesized with and without addition of Eu (Eu-VSOP and VSOP, respectively). MR signal enhancing effects of Eu-VSOP and VSOP were studied in vitro. Cellular uptake of Eu-VSOP and VSOP was examined in RAW264.7 cells. For Eu-VSOP, fluorescence microscopy and spectrophotometry were used. Eu fluorescence was enhanced by means of an antenna system. For VSOP, Prussian blue staining and photometry using the phenanthroline method were applied. Results for both VSOP variants were compared.

Results: Eu-VSOP and VSOP did not differ with respect to MR signal enhancing effects nor to uptake characteristics in the RAW264.7 cell experiments. Fluorescence microscopy detects Eu-VSOP with higher sensitivity compared to light microscopy using Prussian blue staining. In microscopy as well as in the analytical quantification using fluorescence, detection of Eu-VSOP is not contaminated by Fe background.

Conclusions: Doping the VSOP with Eu allows for their improved detection by fluorescence microscopy and quantitative analysis without changing their cellular uptake characteristics or their MR signal enhancing effects and thus would allow for a multimodal approach for studying their pharmacokinetics and biodistribution in experimental research.

Keywords: Iron oxide nanoparticles; MRI; lanthanide luminescence; macrophage; molecular imaging.

MeSH terms

  • Animals
  • Europium
  • Ferric Compounds / chemistry*
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles / analysis*
  • Magnetite Nanoparticles / chemistry
  • Mice
  • Microscopy, Fluorescence* / methods
  • RAW 264.7 Cells / chemistry
  • RAW 264.7 Cells / metabolism


  • Ferric Compounds
  • Magnetite Nanoparticles
  • ferric oxide
  • Europium