Development of superparamagnetic nanoparticles for MRI: Effect of particle size, charge and surface nature on biodistribution

Twelve superparamagnetic Magnetite-Dextran (MD) nanoparticles potentially useful as contrast agents for Magnetic Resonance Imaging (MRI), with different sizes, charges and surface natures, were produced and internally labelled with Fe-59 in order to investigate the effect of their physicochemical properties on their biodistribution in mice. In a first step, neutral MD particles of a size 33-90.6 nm were studied. Next, the influence of charge was investigated with negative and positive particles (MDL, MDD, MDDEAE). The former (-25, -30 mV) were small, around 30 nm in size whereas the latter (+20 mV) were larger (104 nm). The effect of surface nature was evaluated using MD particles coated with polyoxyethylene-polyoxypropylene copolymers (Synperonic(R)): these MDP particles were neutral and larger in size (65.9-76.4 nm). Experiments showed that 20 min post-injection (2 mg Fe/kg), liver uptake was enhanced when the mean diameter increased: 22% for the smallest and 42% for the largest. It was up to 3 x lower for electrically neutral particles than for charged particles. Coated particles presented higher vascular persistence. The diagnostic potential for liver, lymph node or vascular imaging were discussed.