Highly Effective T2 MR Contrast Agent Based on Heparinized Superparamagnetic Iron Oxide Nanoparticles

Abstract

In this study a potential magnetic resonance (MR) T(2) contrast agent was developed systematically based on heparin-coated superparamagnetic iron oxide (SPIO) nanoparticles. Dextran-coated SPIO, which is commercially available as Feridex (R), was prepared for the control group. The size of the crystalline core was adjusted to provide suitable relaxometric properties. Compared to the uncoated SPIO, the heparin or dextran coating provided a better dispersion of SPIO nanoparticles in solution. The zeta potential of the SPIO surface was detected to confirm the polymer coating. The Zeta potential of non-coated SPIO was approximatelt -44 mV, whereas dextran-coated or heparin-coated SPIO was -6.4 and -33.5 mV, respectively. The zeta potential of heparin-coated SPIO was caused by the rich sulfonate group of heparin. In addition, the heparin-coated SPIO showed higher hyponegativity than dextran-coated SPIO. The reason was that the heparin-coated had a lower r(2)/r(1) ratio (18.2) at 1.5-T magnetic resonance imaging (MRI) compared to dextran-coated SPIO (r(2)/r(1) ratio 32.9). Both SPIO nanoparticles can be still suitable for T(2)-weighted MRI because r(2)/r(1) ratio was >10. From the results of in vitro cellular labeling, heparin-coated SPIO was more advantageous for cellular labeling because it could powerfully visualize the cells after a short incubation time (2 h). From these findings, it is possible that heparin-coated SPIO can be used as a good negative contrast agent in clinical MRI.