Ultrasmall Superparamagnetic Iron Oxide Nanoparticles as Nanocarriers for Magnetic Resonance Imaging: Development and <i>In Vivo</i> Characterization
Ge Si, Sudath Hapuarachchige, Dmitri Artemov
Abstract
Ultrasmall superparamagnetic iron oxide nanoparticles (uSPIOs) are attractive platforms for the development of smart contrast agents for magnetic resonance imaging (MRI). Oleic acid-capped uSPIOs are commercially available yet hydrophobic, hindering in vivo applications. A hydrophilic ligand with high affinity toward uSPIO surfaces can render uSPIOs water-soluble, biocompatible, and highly stable under physiological conditions. A small overall hydrodynamic diameter ensures optimal pharmacokinetics, tumor delivery profiles, and, of particular interest, enhanced T1 MR contrasts. In this study, for the first time, we synthesized a ligand that not only fulfills the as-proposed properties but also provides multiple reactive groups for further modifications. The synthesis delivers a facile approach using commercially available reactants, with resultant uSPIO–ligand constructs assembled through a single-step ligand exchange process. Structural and molecular size analyses confirmed size uniformity and small hydrodynamic diameter of the constructs. On average, 43 reactive amine groups were present per uSPIO nanoparticle. Its r1 relaxivity has been tested on a 7 Tesla MR instrument and is comparable to that of the clinically available T1 gadolinium-based contrast agent GBCA (1 vs 3 mM–1 s–1, respectively). A significant decrease in tumor T1 (15%) within 1 h of injection and complete signal recovery after 2 h were detected with a dose of 7 μg Fe/g mouse. The agent also has high r2 relaxivity and can be used for T2 contrast-enhanced MRI. Taken together, good relaxation and delivery properties and the presence of multiple surface reactive groups can facilitate its application as a universal MRI-compatible nanocarrier platform.