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

Abstract

本文主要开发了一种谷胱甘肽（GSH）和H2O2双响应信号反转磁共振成像造影剂SPION@DMSN@PEG，该造影剂主要由可降解介孔二氧化硅纳米粒子（DMSN）和超顺磁性氧化铁纳米粒子（SPION）组成。小鼠体内MRI成像研究显示，该造影剂可在肿瘤部位实现对肿瘤的T2加权成像，随着DMSN在酸性且富含谷胱甘肽和过氧化氢的肿瘤微环境条件下降解，造影剂可从T2信号向T1信号转变，最终转变为T1信号3002 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 T 2 to T 1 contrast enhancement in vivo still remains a challenge. Here, we demonstrated the synthesis of a glutathione (GSH) and H 2 O 2 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 T 2 -weighted imaging in tumor site, and enabled an efficacious switch to T 1 -weighted imaging upon the GSH- and H 2 O 2 -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 T 2 -weighted imaging up to 2 h post-intravenous injection, which was succeeded by T 1 -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. A glutathione (GSH) and H 2 O 2 dual-responsive “signal inversion” contrast agent (SPION@DMSN@PEG) is synthesized in this work, which achieves T 2 -weighted magnetic resonance imaging (MRI) in tumor site, and enables an efficacious switch to T 1 -weighted MRI upon the GSH- or H 2 O 2 -mediated degradation of DMSN.