Superparamagnetic iron oxide nanocrystals (SPIONs) are a biocompatible, FDA-approved, and gadolinium-free alternative to standard clinical magnetic resonance imaging (MRI) contrast agents. Their tunable magnetic and physiochemical properties make SPIONs promising contrast agents for advanced MRI applications in molecular imaging. For more comprehensive clinical translation, these techniques require highly sensitive contrast agents with excellent magnetic and colloidal stability. Therefore, a major challenge to optimizing SPION performance is understanding the relationship between their various physiochemical parameters and relaxation dynamics. Here, the size- and surface coating-dependent T2 relaxivity (r2) and colloidal and magnetic stability of iron oxide nanocrystals are probed. Synthesized iron oxide nanocrystals are monodispersed, size-tunable (4 – 33 nm), and demonstrate excellent colloidal and r2 stability across a range of surface coatings and physiologically relevant conditions. The largest r2 (510 mM-1 s-1) is achieved with a large core size (33 nm) and thin surface coating (oleic acid bilayer). Notably, grafting density is employed as a novel metric to clarify complex trends in surface coating-dependent data found here and in the literature. Nanocrystals with thicker coatings can retain high r2 (&gt; 300 mM-1 s-1) by maintaining a reduced grafting density. Nanocrystals demonstrate size- and surface coating-dependent cytotoxicity in human dermal fibroblasts (HDF) with no significant cytotoxicity at iron concentrations as high as 6,000 µM. These data help inform the rational design of highly sensitive, biocompatible, robust, and smart T2 SPION contrast agents for molecular imaging.

Optimizing the T2 relaxation dynamics of iron oxide nanocrystals for the rational design of advanced MRI contrast agents: size and surface engineering

ACS Spring 2022

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