Sensitive T2 MRI Contrast Agents from the Rational Design of Iron Oxide Nanoparticle Surface Coatings

Iron oxide nanoparticles are an FDA-approved and gadolinium-free alternative to conventional magnetic resonance imaging (MRI) contrast agents. While their magnetic cores are responsible for T2 contrast, the nonmagnetic polymers at the particle interfaces can affect the diffusion of bulk water near the particles. We show here how this interaction can alter the relaxation dynamics of water protons and, consequently, the nanoparticle's contrast performance. Libraries of iron oxide nanocrystals of different core diameters and surface coatings can form biocompatible, non-cytotoxic, and colloidally stable suspen-sions with excellent MRI properties. Both the grafting density and thickness of polymer coatings influence the amount of time water protons spend around a nanoparticle and thus their contrast agent performance. Characterization of the diameter-dependent contrast performance of these materials revealed that nanoparticles with dense, hydrophilic polymer coatings reached the static dephasing regime, and optimal T2 relaxivity, at smaller dimensions than other systems. We rationalized that such coatings offered a slow compartment for water diffusion near the magnetic particle, resulting in an effective diffusion constant lower than bulk water. By manipulating the surface coating and core diameter together, we could generate a material with one of the largest T2 relaxivities ever reported (510 mM-1 s-1) for an isolated nanocrystal. This conceptual framework can explain the complex structure-performance trends of this class of T2 contrast agents and those already reported in the existing literature. Water diffusion at iron oxide nanocrystals (IONCs) interfaces is an essential consideration in designing sensitive and possibly responsive T2 MRI contrast agents.