A screening paradigm for the design of improved polymer-coated superparamagnetic iron oxide nanoparticles

Abstract

Polymer-coated superparamagnetic iron oxide nanoparticles (NPs) have been used for a variety of biomedical applications, including as MRI contrast agents, for the treatment of iron anemias, and for ex vivo labeling of the cells used in cell-based therapies so that they can be tracked by MRI. Here we describe a three-stage screening paradigm to develop high potency (i.e., high relaxivity), stable, polymer-coated superparamagnetic iron oxide NPs. Each screen examined different facets of the interaction between iron oxides and polymers. First, an Ion Challenge Screen assessed whether a polymer interacted with the surface of the iron oxide. Second, a Synthesis Optimization Screen examined whether polymers that passed the Ion Challenge Screen were compatible with the synthetic method used to make NPs, and optimized the synthetic method for each polymer. Finally, a Heat Stress/Stability Screen assessed the stability of the optimized polymer-coated superparamagnetic iron oxides that passed the Synthesis Optimization Screen. A carboxymethyl dextran-coated superparamagnetic iron oxide nanoparticle (CMD-NP) with a transverse relaxivity (R₂) of 271 mM⁻¹ s⁻¹ and a diameter of 47 nm by dynamic light scattering was obtained. A second NP, a carboxymethyl polyvinyl alcohol-coated nanoparticle (CMPVA-NP) had an R₂ of 119 and diameter of 37 nm, but was less stable to heat stress than the CMD-NP. The CMD-NP is a polymer-coated superparamagnetic iron oxide NP with improved relaxivity and high stability achieved without the crosslinking procedure used in our cross-linked iron oxide (CLIO) NP.