Time‐Dependent T₁–T₂ Switchable Magnetic Resonance Imaging Realized by c(RGDyK) Modified Ultrasmall Fe₃O₄ Nanoprobes

Abstract To achieve the accurate diagnosis of tumor with the magnetic resonance imaging (MRI), nanomaterials‐based contrast agents are developed rapidly. Here, a tumor targeting nanoprobe of c(RGDyK) modified ultrasmall sized iron oxide is reported with high saturation magnetization and high T₁‐weighted imaging capability, attributed to a large number of paramagnetic centers on the surface of nanoprobes and rapid water proton exchange rate (inner sphere model), as well as strong superparamagnetism (outer sphere model). These nanoprobes could actively target and gradually accumulate at the tumor site with a time‐dependent T₁–T₂ contrast enhancement imaging effect. In in vivo MRI experiments, the nanoprobes exhibit the best T₁ contrast enhancement at 30 min after intravenous administration, followed by gradually vanishing and generating T₂ contrast enhancement with increasing time at tumor site. This is likely due to time‐dependent nanoprobes aggregation in tumor, in good agreement with in vitro experiment where aggregated nanoprobes display larger r₂/r₁ value (19.1) than that of the dispersed nanoprobes (2.8). This dynamic property is completely different from other T₁‐T₂ dual‐modal nanoprobes which commonly exhibit the T₁‐ and T₂‐weighted enhancement effect at the same time. To sum up, these c(RGDyK) modified ultrasmall Fe₃O₄ nanoprobes have significant potential to improve the diagnostic accuracy and sensitivity in MRI.