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Targeted T1 Magnetic Resonance Imaging Contrast Enhancement with Extraordinarily Small CoFe2O4 Nanoparticles

2019, Piché, Dominique, Tavernaro, Isabella, Fleddermann, Jana, Lozano, Juan G., Varambhia, Aakash, Maguire, Mahon L., Koch, Marcus, Ukai, Tomofumi, Hernández Rodríguez, Armando J., Jones, Lewys, Dillon, Frank, Reyes Molina, Israel, Mitzutani, Mai, González Dalmau, Evelio R., Maekawa, Toru, Nellist, Peter D., Kraegeloh, Annette, Grobert, Nicole

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 r2/r1 ratio suitable for a T1 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 T1 MRI. Our study demonstrates the potential of ESCIoNs as T1 MRI contrast agents.