Controlled aggregation of superparamagnetic iron oxide nanoparticles for the development of molecular magnetic resonance imaging probes

A method for synthesizing superparamagnetic iron oxide (SPIO) multi-nanoparticle aggregates as molecular magnetic resonance imaging (MRI) contrast agents is described. The approach utilizes organic acid/base interactions in the colloid to induce highly controllable nanoparticle aggregation. Monodisperse aggregates with diameters as large as 100 nm are synthesized by manipulating the interfacial surface chemistry of the SPIO nanoparticles in tetrahydrofuran solvent. Subsequent phospholipid micelle encapsulation yields micellar multi-SPIO (mmSPIO) aggregates with enhanced T₂ relaxivity (368.0 s^-1 mmol^-1 Fe) as compared to micellar single particle SPIO (302.0 s^-1 mmol^-1 Fe). mmSPIO conjugated to anti-CA125 monoclonal antibodies were incubated with ovarian carcinoma cell lines to demonstrate targeted in vitro molecular MRI, resulting in a 66% shortening in T₂ time for CA125 positive NIH:OVCAR-3 cells and a less than 3% change in T₂ time for CA125 negative SK-OV-3 cells. The controllable aggregation of mmSPIO shows potential for the development of molecular MRI contrast agents with optimal sizes for specific diagnostic imaging applications.