Preparation, Characterization And Application Of A Novel Liver-Targeted Super-Ultrasmall Superparamagnetic Iron Oxide Nanoparticle (SUSPIO)

In the last decade, superparamagnetic iron oxide (SPIO) nanoparticles coated with appropriate surface chemistry have been widely investigated for their potential applications in biomedicine. The applications being actively pursued include magnetic resonance imaging (MRI), drug delivery, tissue repair, hyperthermia in the treatment of malignant tumors and magnetofection. For in vivo applications, the nanoparticles should be sufficient small, stable at physiological condition and present superparamagnetic behavior at room temperature.Studies have been shown that the size of iron oxide particle and the coating have a notable influence on its magnetic property and cytotoxicity. Most of the developed SPIO and ultrasmall SPIO nanoparticles to date were stabilized by dextran or its derivatives with overall size 30~50nm. Generally speaking, larger polymer-coated SPIO particles (about 50 nm) were mainly trapped in the liver, while smaller sizes (about 30 nm) normally were useful for imaging the lymph node systems and bone marrow. All SPIO particles presently undergoing preclinical or clinical testing are coated with polymeric material (eg, dextran, carboxydextran, polyethylene glycol). Studies have been shown that dextran limits the tolerance of the compound, which can therefore only be administered as a slow infusion. In addition, all polymers used, even the well-tolerated polyethylene glycol, have limitations in tissue distribution, penetration, metabolic clearance and produce adverse reactions. Although non-polymers coated superparamagnetic nanoparticles have been investigated in MR angiography in recent several reports, relatively little work has been carried out on the nanoparticles with overall size smaller than 10nm in terms of size.In this study, we describe here a novel non-polymer coated superparamagnetic nanoparticle with an overall size of 5nm around. The coated non-polymer was a liver-born methylating agent with active surface property. The SUSPIO exhibited excellent biocompatibility both in vitro and in vivo and successfully used for MRI detection of hepatocellular carcinoma (HCC) nodules varied 1-25mm in diameters in rat. Our data demonstrated this magnetite nanoparticle would have obvious potential in molecular imaging for biomedical research and clinical diagnosis as a novel MR contrast agent.