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

Abstract

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 ⁵⁹Fe 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 × 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.

Key Words:

• Nanoparticles
• biodistribution
• size
• charge
• surface
• magnetic resonance
• superparamagnetic