Redox-Mediated Disassembly to Build Activatable Trimodal Probe for Molecular Imaging of Biothiols

Activatable multimodal probes that show enhancement of multiplex imaging signals upon interaction with their specific molecular target have become powerful tools for rapid and precise imaging of biological processes. Herein, we report a stimuli-responsive disassembly approach to construct a redox-activatable fluorescence/F-19-MRS/H-1-MRI triple-functional probe 1. The small molecule probe 1 itself has a high propensity to self-assemble into nanoparticles with quenched fluorescence, attenuated F-19-MRS signal, and high H-1-MRI contrast. Biothiols that are abundant in reducing biological environment were able to cleave the disulfide bond in probe 1 to induce disassembly of the nanoparticles and lead to fluorescence activation (similar to 70-fold), F-19-MRS signal amplification (similar to 30-fold) and significant r(1) relaxivity reduction (similar to 68% at 0.5 T). Molecular imaging of reducing environment in live cells and in vivo was realized using probe 1. This approach could facilitate the development of other stimuli-responsive trimodal probes for molecular imaging.