Atomically precise multi-domain GdxFe3−xO4 nanoclusters with modulated contrast properties for T2-weighted magnetic resonance imaging of early orthotopic cancer

The use of multi-domain magnetic iron oxide nanoclusters (MMIONs) as Magnetic resonance imaging (MRI) contrast agent is facing problems of strong ferromagnetism and thus weak T2 contrast ability. The doping of Gd ions holds potential to solve these problems by reducing ferromagnetism and enhancing transverse relaxivity (r2), but the exact role of doping in modulating the contrast properties remain unknown. Herein, we prepared a series of atomically precise GdxFe3−xO4 nanoclusters and systematically explored the effect of Gd doping on tuning their morphology, magnetic property, and r2 value. After the doping of Gd ions, the specific surface area of GdxFe3−xO4 nanoclusters significantly increased, and meanwhile, the magnetic property of GdxFe3-xO4 nanoclusters transformed from ferromagnetism to superparamagnetism, which led to stronger T2 contrast. Specifically, the highest r2 value was obtained at 488 mM−1s−1 (7.0 T) for Gd0.072Fe2.928O4 nanocluster, four times higher than that for pristine Fe3O4 (110 mM−1s−1). For potential applications, we validated the outstanding contrast of Gd0.018Fe2.982O4 nanocluster (r2 = 481 mM−1s−1 at 7.0 T) to diagnose early orthotopic cancer in mice. This work opens up a new avenue for the development of atomically precise Gd-doped MMIONs as efficient T2-weighted MRI contrast agents.