Targeted T(1) Magnetic Resonance Imaging Contrast Enhancement with Extraordinarily Small CoFe(2)O(4) Nanoparticles

[Image: see text] Extraordinarily small (2.4 nm) cobalt ferrite nanoparticles (ESCIoNs) were synthesized by a one-pot thermal decomposition approach to study their potential as magnetic resonance imaging (MRI) contrast agents. Fine size control was achieved using oleylamine alone, and annular dark-field scanning transmission electron microscopy revealed highly crystalline cubic spinel particles with atomic resolution. Ligand exchange with dimercaptosuccinic acid rendered the particles stable in physiological conditions with a hydrodynamic diameter of 12 nm. The particles displayed superparamagnetic properties and a low r(2)/r(1) ratio suitable for a T(1) contrast agent. The particles were functionalized with bile acid, which improved biocompatibility by significant reduction of reactive oxygen species generation and is a first step toward liver-targeted T(1) MRI. Our study demonstrates the potential of ESCIoNs as T(1) MRI contrast agents.