Ultrasmall superparamagnetic Fe3O4 nanoparticles (USIRONs) were synthesized by a novel, easily scalable chemical reduction of colloidal iron hydroxide under hydrothermal conditions. The average crystallite size (5.1 ± 0.5 nm) and good crystallinity of the samples were supported by HR-TEM analysis and the saturation magnetization value (47 emu g–1). Vitamin C, used as a chemical reducing agent, also served as a capping agent in the oxidized form (dehydroascorbic acid, DHAA) to impart nanoparticles with exceptional solubility and stability in water, PBS buffer, and cell culture medium. Detailed physicochemical analysis of the USIRON suspensions provided insight into the magnetic ordering phenomena within the colloid, arising from the formation of uniform clusters displaying a hydrodynamic size of 41 nm. Phantom experiments on the contrast agent (clinical 3 T MRI scanner) revealed an enhanced r2/r1 ratio of 36.4 (r1= 5 s–1 mM–1 and r2= 182 s–1 mM–1) when compared to the clinically approved agents. The potential of the DHAA-Fe3O4 nanoparticles as negative contrast agents for MRI with optimal hydrodynamic size for extended blood circulation times was confirmed by strong contrast observed in T2- and T2*-weighted images. The cell tests performed with primary human immune-competent cells confirmed the excellent biocompatibility of USIRONs.

Water-Soluble Superparamagnetic Magnetite Nanoparticles with Biocompatible Coating for Enhanced Magnetic Resonance Imaging