Abstract

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/19F-MRS/1H-MRI triple-functional probe 1. The small molecule probe 1 itself has a high propensity to self-assemble into nanoparticles with quenched fluorescence, attenuated 19F-MRS signal, and high 1H-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 (∼70-fold), 19F-MRS signal amplification (∼30-fold) and significant r1 relaxivity reduction (∼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.

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