A Smart Glutathione and H2O2 Dual-Responsive Signal Inversion Magnetic Resonance Imaging Contrast Agent for Tumor Diagnosis

Abstract Accurate bioimaging of internal body tissues plays a key role in achieving precise medical diagnosis. Magnetic resonance imaging (MRI) as one of the clinically used bioimaging modalities is largely hampered by the occurrence of false-positive imaging (artifacts). The use of contrast agents has tremendously contributed to the improvement of the accuracy of MRI, however, developing a dual-responsive contrast agent that capable of effectively switching from T2 to T1 contrast enhancement in vivo still remains a challenge. Here, we demonstrated the synthesis of a glutathione (GSH) and H2O2 dual-responsive “signal inversion” contrast agent, which mainly comprised of superparamagnetic iron oxide nanoparticles (SPION) and degradable mesoporous silica nanoparticles (DMSN). The contrast agent achieved T2-weighted imaging in tumor site, and enabled an efficacious switch to T1-weighted imaging upon the GSH- and H2O2-mediated degradation of DMSN. The characteristics of the signal transformation largely reduced the artifacts to enhance the accuracy of MRI. Interestingly, the in vivo evaluations revealed prominence of the T2-weighted imaging up to 2 h post-intravenous injection, which was succeeded by T1-weighted imaging that gradually increased with time and became dominant after 24 h. It was therefore expected that the findings shown in this work would guide the development of other contrast agents alike for more robust and accurate bioimaging by using MRI.