Facile non-hydrothermal synthesis of oligosaccharide coated sub-5 nm magnetic iron oxide nanoparticles with dual MRI contrast enhancement effects

Ultrafine sub-5 nm magnetic iron oxide nanoparticles coated with oligosaccharides (SIO) with dual T-1-T-2 weighted contrast enhancing effects and fast clearance have been developed as magnetic resonance imaging (MRI) contrast agents. Excellent water solubility, biocompatibility and high stability of such sub-5 nm SIO nanoparticles were achieved by using the "in situ polymerization" coating method, which enables glucose to form oligosaccharides directly on the surface of hydrophobic iron oxide nanocrystals. Reported ultrafine SIO nanoparticles exhibit a longitudinal relaxivity (r(1)) of 4.1 mM(-1) s(-1) and a r(1)/r(2) ratio of 0.25 at 3 T (clinical field strength), rendering improved T-1 or "brighter" contrast enhancement in T-1-weighted MRI in addition to typical T-2 or "darkening" contrast of conventional iron oxide nanoparticles. Such dual contrast effects can be demonstrated by liver imaging with T-2 "darkening" contrast in the liver parenchyma but T-1 "bright" contrast in the hepatic vasculature. More importantly, this new class of ultrafine sub-5 nm iron oxide nanoparticles showed much faster body clearance than those with larger sizes, promising better safety for clinical applications.