Fe3O4 assembly for tumor accurate diagnosis by endogenous GSH responsive T2/T1 magnetic relaxation conversion

Abstract

Superparamagnetic iron oxide nanoparticles with high magnetization strength and good biological safety have been widely used as magnetic resonance imaging (MRI) contrast agents for tumors. However, the accuracy of tumor diagnosis is still low due to the lack of tumor targeting and the interference signals from normal tissues. Endogenous substances in tumor (such as high levels of GSH and pH) stimuli-responsive contrast agents could offer higher sensitivity for tumor diagnosis. Herein, based on the characteristic of overexpression of GSH in tumors, we propose an ultra-small Fe₃O₄ assembly as an endogenous GSH responsive MRI contrast agent. The ultra-small superparamagnetic Fe₃O₄ are bonded to the crosslinker cystamine to synthesize Fe₃O₄ nanoclusters, which exhibit a T₂ imaging effect. When the contrast agent reaches the tumor tissue, the disulfide bond in cystamine is induced by GSH to break, the Fe₃O₄ nanoclusters are disassembled into ultra-small Fe₃O₄ nanoparticles, and the relaxation signal changes from T₂ to T₁, which is helpful for accurate diagnosis of tumors. In vivo experiments have shown that Fe₃O₄ nanoclusters can rapidly respond to overexpressed GSH in tumor sites for T₂/T₁ switchable imaging. This work not only designed an endogenous GSH responsive platform through simple synthesis methods, but also improved the accuracy of tumor diagnosis through the transformation of T₂/T₁ MRI signals.