Self-assembly of iron oxide nanoparticles for microvascular magnetic resonance imaging

Abstract

Iron-oxide nanoparticles (IONPs) are clinically used as stable contrast agents for magnetic resonance imaging. However, their application in microvascular imaging is limited because of their rapid diffusion across soft tissues and high accumulation in the liver. In this study, we present a self-assembled IONPs based contrast agent for cerebrovascular imaging. The IONPs were modified with fluorescein-conjugated 4-arm polyethylene glycol to prepare 4P-F-IONPs. Light-scattering analysis revealed that 4P-F-IONPs formed nanorod-like structures through self-assembly via fluorescein conjugation. Pharmacokinetic studies indicated longer blood circulation and reduced organ diffusion for the self-assembled nanorod contrast agent compared with pristine IONPs. Furthermore, microvasculature as small as 400 μm in diameter was clearly visualized after intravenous injection in a rat model. In contrast, the signals were not enhanced when 4P-IONPs (without fluorescein conjugation) were injected. These results suggest that fluorescein conjugation induces a structural transition in IONPs, which reduces contrast diffusion across micro-vessels and enhances the MR signals in the microvasculature.