CBT-Cys click reaction for optical bioimaging in vivo

Abstract

Derived from the D-luciferin regeneration pathway in firefly body, the click condensation reaction between 2-cyanobenzothiazole (CBT) and D-cysteine (Cys) (CBT-Cys click reaction) possesses unique advantages, including superior biocompatibility, high second order reaction rate, and metal-free mild conditions, emerging as a powerful bioorthogonal tool for a variety of chemical biological applications. Moreover, owing to its programmable controllability (e.g., pH, reduction, or enzyme), CBT-Cys click reaction is exploited to fabricate stimuli-activatable imaging probes with self-assembling behaviors in physiological context. At stimuli-rich pathological lesions of interest, these probes undergo CBT-Cys click reaction to form cyclic dimers/oligomers or linear polymers, and further self-assemble into nanostructures. The in situ formed nanostructures promote the selective accumulation and retention of imaging agent cargos at pathological lesions, thus enabling precise and enhanced in vivo imaging of diseases (especially tumors). To address the significance and recent breakthroughs of smart CBT-Cys probes for enhanced optical imaging of tumors/other diseases, we herein propose this mini-review, in which advances (particularly in recent 5 years) and potential challenges (or chances) in this field are emphasized.