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

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.