Physicochemical characterization of ultrasmall superparamagnetic iron oxide particles (USPIO) for biomedical application as MRI contrast agents

Abstract

Ultrasmall superparamagnetic iron oxide (USPIO) particles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging. The coatings surrounding the USPIO inorganic core play a major role in both the in vitro stability and, over all, USPIO's in vivo fate. Different physicochemical properties such as final size, surface charge and coating density are key factors in this respect. Up to now no precise structure--activity relationship has been described to predict entirely the USPIOs stability, as well as their pharmacokinetics and their safety. This review is focused on both the classical and the latest available techniques allowing a better insight in the magnetic core structure and the organic surface of these particles. Concurrently, this work clearly shows the difficulty to obtain a complete physicochemical characterization of USPIOs particles owing to their small dimensions, reaching the analytical resolution limits of many commercial instruments. An extended characterization is therefore necessary to improve the understanding of the properties of USPIOs when dispersed in an aqueous environment and to set the specifications and limits for their conception.

Figure 1

The figure shows how the number of atoms in the sphere volume and the one in a superficial layer differently increase growing the nanoparticle dimension. The ratio, in the inset, shows that the number of atoms in the surface layer is prevalent in the smallest nanoparticles.

Figure 2

(a) A model of SAMs grafted onto nanoparticle surface, the active part being a carboxylate carrying a generic terminal groups R. (b) A detail of the nanoparticle showing an interaction schema between carboxylate SAMS and the first layer atoms of the iron oxide surface.

Figure 3

(a) A nanoparticle grafted with long-chain fatty acids self-assembled monolayers without R functional groups. (b) A scheme of possible fatty acids (alpha linoleic acid) to graft into iron oxide surface particles.