Highly effective T2 MR contrast agent based on heparinized superparamagnetic iron oxide nanoparticles

In this study a potential magnetic resonance (MR) T2 contrast agent was developed systematically based on heparin-coated superparamagnetic iron oxide (SPIO) nanoparticles. Dextran-coated SPIO, which is commercially available as Feridex®, 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 r2/r1 ratio (18.2) at 1.5-T magnetic resonance imaging (MRI) compared to dextran-coated SPIO (r2/r1 ratio 32.9). Both SPIO nanoparticles can be still suitable for T2-weighted MRI because r2/r1 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.