Endothelial cell-derived microparticles loaded with iron oxide nanoparticles: feasibility of MR imaging monitoring in mice

Radiology. 2012 Apr;263(1):169-78. doi: 10.1148/radiol.11111329. Epub 2012 Feb 13.

Abstract

Purpose: To assess the feasibility of loading iron oxide nanoparticles in endothelial microparticles (EMPs), thereby enabling their noninvasive monitoring with magnetic resonance (MR) imaging in mice.

Materials and methods: Experiments were approved by the French Ministry of Agriculture. Endothelial cells, first labeled with anionic superparamagnetic nanoparticles, were stimulated to generate EMPs, carrying the nanoparticles in their inner compartment. C57BL/6 mice received an intravenous injection of nanoparticle-loaded EMPs, free nanoparticles, or the supernatant of nanoparticle-loaded EMPs. A 1-week follow-up was performed with a 4.7-T MR imaging device by using a gradient-echo sequence for imaging spleen, liver, and kidney and a radial very-short-echo time sequence for lung imaging. Comparisons were performed by using the Student t test.

Results: The signal intensity loss induced by nanoparticle-loaded EMPs or free nanoparticles was readily detected within 5 minutes after injection in the liver and spleen, with a more pronounced effect in the spleen for the magnetic EMPs. The kinetics of signal intensity attenuation differed for nanoparticle-loaded EMPs and free nanoparticles. No signal intensity changes were observed in mice injected with the supernatant of nanoparticle-loaded EMPs, confirming that cells had not released free nanoparticles, but only in association with EMPs. The results were confirmed by using Perls staining and immunofluorescence analysis.

Conclusion: The strategy to generate EMPs with magnetic properties allowed noninvasive MR imaging assessment and follow-up of EMPs and opens perspectives for imaging the implications of these cellular vectors in diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell-Derived Microparticles*
  • Contrast Media / pharmacokinetics*
  • Drug Delivery Systems
  • Electron Spin Resonance Spectroscopy
  • Endothelial Cells
  • Feasibility Studies
  • Ferric Compounds / pharmacokinetics*
  • Flow Cytometry
  • Liver / cytology*
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Microscopy, Electron, Transmission
  • Nanoparticles*
  • Spleen / cytology*

Substances

  • Contrast Media
  • Ferric Compounds