Gadolinium oxide nanocrystals with a sulfonated polymer coating can be applied as MRI contrast agents. One significant challenge faced in designing a nanocrystal as a T1 MRI agent, as opposed to a T2 contrast agent, is the requirement that water must be able to come within several angstroms of surface gadoliniun atoms. Successful materials must then possess a surface which both prevents aggregation in biological media and ensures surface accessibility. Here we exploit the plate-like geometry of gadolinium oxide nanocrystals to achieve these two aims. These nanocrystals are formed at high temperature in organic solvents and subsequently phase transferred into biological media using a sulfonic acid co-polymer. The crystals’ anisotropic shape provides gadolinium atoms on the thin plate edges which remain uncoated and thus available to water. The relaxivities of these materials are one order of magnitude (15 times) larger than commercial T1 contrast agents and other gadolinium-containing nanoparticles. The magnetic field dependence of their relaxation rates and the relatively weak size dependence of their relaxivity suggest that inner-sphere water relaxation at the edges of the nanocrystal are responsible for the high relaxation rates. . The nanocrystals show no appreciable in-vitro cellular toxicity even though they are readily taken up by cells and retain their functionality in the intracellular environment. In vivo the nanocrystals have comparable blood circulation life time compared to molecular gadolinium agents and are cleared by the hepatobiliary system. Their cellular uptake enables MRI imaging to be applied to cellular detection as illustrated in the differentiation of non-alcoholic fatty liver disease in mice.

Gadolinium oxide nanocrystals as T1 MRI contrast agents: Balancing colloidal stability with surface accessibility

253rd National Meeting (2017)

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