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 (59)Fe 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: 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.