Ultrasmall Superparamagnetic Iron Oxide Nanoparticles Coated with Fucoidan for Molecular MRI of Intraluminal Thrombus

Abstract

Aim: We have designed ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles associated with fucoidan (USPOI-FUCO), a natural sulfated polysaccharide with high affinity for activated platelets, to visualize by MRI arterial thrombi. Materials & methods: USPIOs were prepared and sizes, zeta-potentials and relaxivities were measured. Elastase perfusion in the infrarenal aorta of Wistar rats induced intraluminal thrombus. They were scanned on 4.7 T MRI before and after injection of USPIO-FUCO or USPIO coated with anionic dextran. Results: Surface plasmon resonance evidenced that fucoidan and USPIO-FUCO bind in vitro to immobilized P-selectin. All intraluminal hyposignals detected by MRI after injection of USPIO-FUCO on animals (13 out of 13) were correlated by histology with thrombi, whereas none could be identified with control USPIOs (0 out of 7). No signal was seen in absence of thrombus. Thrombi by MRI were correlated with P-selectin immunostaining and USPIO detection by electron microscopy. Conclusion: In vivo thrombi can thus be evidenced by MRI with USPIO-FUCO.

Original submitted 8 July 2013; Revised submitted 4 March 2014

Keywords::

• aneurysm
• iron oxide nanoparticle
• MRI
• P-selectin
• thrombus

Financial & competing interests disclosure

This study was supported by the ’Fondation de l’Avenir’ to J-B Michel, ’FRM/SGAM Prix innovation Cardiovasculaire’ to D Letourneur, and the FUI/OSEO/CG93 for IMOVA project with Medicen. Inserm U1148 is also supported by the EU through the integrated project NanoAthero (NMP-2012–309820), and the Agence Nationale de la Recherche (ANR Blanc Nanosciences Ferimage; ANR RPIB FucoThrombo; ANR LabCom FucoChem). M Suzuki was supported by a grant from Ministère des Affaires Etrangères et Européennes from Japan. We thank O Clément and C-A Cuenod at Paris-Centre de Recherche Cardiovasculaire (PARCC)-INSERM U970 for 4.7T MRI experiments, O Brinza (Laboratoire des Sciences des Procédés et des Matériaux; Villetaneuse, France) for his technical assistance for electron microscopy, E Gueneau from GE Healthcare (Velizy, France) for surface plasmon resonance experiments on X100 and M Osborne-Pellegrin for editorial assistance. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

This study was supported by the ’Fondation de l’Avenir’ to J-B Michel, ’FRM/SGAM Prix innovation Cardiovasculaire’ to D Letourneur, and the FUI/OSEO/CG93 for IMOVA project with Medicen. Inserm U1148 is also supported by the EU through the integrated project NanoAthero (NMP-2012–309820), and the Agence Nationale de la Recherche (ANR Blanc Nanosciences Ferimage; ANR RPIB FucoThrombo; ANR LabCom FucoChem). M Suzuki was supported by a grant from Ministère des Affaires Etrangères et Européennes from Japan. We thank O Clément and C-A Cuenod at Paris-Centre de Recherche Cardiovasculaire (PARCC)-INSERM U970 for 4.7T MRI experiments, O Brinza (Laboratoire des Sciences des Procédés et des Matériaux; Villetaneuse, France) for his technical assistance for electron microscopy, E Gueneau from GE Healthcare (Velizy, France) for surface plasmon resonance experiments on X100 and M Osborne-Pellegrin for editorial assistance. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.