Quasi-amorphous and Hierarchical Fe₂O₃ Supraparticles: Active <i>T</i>₁-Weighted Magnetic Resonance Imaging <i>in Vivo</i> and Renal Clearance.

Abstract

The exploration of magnetic resonance imaging (MRI) agents possessing excellent performances and high biosafety is of great importance for both fundamental science research and biomedical applications. In this study, we present that monodisperse Fe₂O₃ supraparticles (SPs) can act as <i>T</i>₁-weighted MRI agents, which not only possess a distinct off-on MRI switch in the tumor microenvironment but also are readily excreted from living bodies due to its quasi-amorphous structure and hierarchical topology design. First, the Fe₂O₃ SPs have a surface-to-volume ratio obviously smaller than that of their building blocks by means of self-assembly processes, which, on the one hand, causes a rather low <i>r</i>₁ relaxivity (0.19 mM^-1 s^-1) and, on the other hand, can effectively prevent their aggregation after intravenous injection. Second, the Fe₂O₃ SPs have a dramatic disassembly/degradation-induced active <i>T</i>₁-weighted signal readout (more than 6 times the <i>r</i>₁ value enhancement and about 20 times the <i>r</i>₂/<i>r</i>₁ ratio decrease) in the tumor microenvironment, resulting in a high signal-to-noise ratio for imaging performances. Therefore, they possess excellent <i>in vivo</i> imaging capacity, even with a tumor size as small as 5 mm³. Third, the disassembled/decomposed behaviors of the Fe₂O₃ SPs facilitate their timely clearance/excretion from living bodies. In particular, they exhibit distinct renal clearance behavior without any kidney damage with the right dosage. Fourth, the favorable biodegradability of the as-prepared Fe₂O₃ SPs can further relieve the concerns about the unclear biological effects, particularly on nanomaterials, in general.