Coating influence on inner shell water exchange: An underinvestigated major contributor to SPIONs relaxation properties

Superparamagnetic iron oxide nanoparticles (SPIONs) are heavily studied as potential MRI contrast enhancing agents. Every year, novel coatings are reported which yield large increases in relaxivity compared to similar particles. However, the reason for the increased performance is not always well understood mechanistically. In this review, we attempt to relate these advances back to fundamental models of relaxivity, developed for chelated metal ions, primarily gadolinium. We focus most closely on the three-shell model which considers the relaxation of surface-bound, entrained, and bulk water molecules as three distinct contributions to total relaxation. Because SPIONs are larger, more complex, and entrain significantly more water than gadolinium-based contrast agents, we consider how to adapt the application of classical models to SPIONs in a predictive manner. By carefully considering models and previous results, a qualitative model of entrained water interactions emerges, based primarily on the contributions of core size, coating thickness, density, and hydrophilicity.