Succinylated heparin monolayer coating vastly increases superparamagnetic iron oxide nanoparticle T2 proton relaxivity.

Superparamagnetic iron oxide nanoparticles (SPIONs) have a history of clinical use as contrast agents in T2 weighted MRI, though relatively low T2 relaxivity has caused them to fall out of favor as new faster MRI techniques have gained prominence. We demonstrate that SPIONs coated with a monolayer of succinylated heparin (Su-HP-SPIONs) exhibit over four-fold increased T2 relaxivity (460 mM-1 s-1) as compared to the clinically approved SPION-based contrast agent Feridex (98.3 mM-1 s-1) due to greatly increased water interaction from increased hydrophilicity and thinner coating as supported by our proposed parametric model. In vivo, the performance increase of the Su-HP-SPIONs in T2 MRI imaging of xenograft tumors is ten-fold that of our in-house synthesized Feridex analogue, due to better tumor localization from the smaller size imparted by the thinner coating. In addition to these significantly improved magnetic properties, the succinylated heparin coating also exhibits favorable synthetic reproducibility, solution stability, and biocompatibility. These findings demonstrate the untapped potential of SPIONs as possible high performance clinical T2 contrast agents.