Cathepsin B Turning Bioluminescence “On” for Tumor Imaging

Abstract

Cathepsin B (CTSB) is a lysosomal protease, and several human cancers are reported highly expressing CTSB. Many optical methods have been developed for CTSB detection but not a bioluminescence (BL) probe. Herein, a CTSB-specific bioluminescence probe Val-Cit-AL was rationally designed for selectively sensing CTSB activity in vitro with a 67-fold “Turn-On” of BL intensity and an excellent limit of detection. Inhibitory experiments indicated that Val-Cit-AL is capable of sensing CTSB activity in living cells and tumors. We anticipate that Val-Cit-AL might be applied to diagnose CTSB-related diseases in rodent models or evaluate CTSB roles in more biological processes in the near future.

Peptide probes for proteases – innovations and applications for monitoring proteolytic activity

“…enzyme or analyte). This strategy has been adopted to develop luminogenic probes for proteases such as cathepsin B ( 46 ), 162 chymotrypsin ( 47 ), 163 carboxypeptidases A and B ( 48 ), 164 Caspase-1 ( 49 ) 165 and furin ( 50 and 51 ) 166 (Fig. 15a).…”

Constructing firefly luciferin bioluminescence probes for in vivo imaging

“…Val-Cit-D-aminoluciferin (Val-Cit-AL) was designed to detect the activity of cathepsin B for diagnosing cancer. 58 Levulinic acid can be selectively recognized by sulfite. The nucleophilic attack of SO 3 2− cleaved the C-O bond, and the levulinic acid head cyclized the five-membered lactone ring.…”

Most recent advances on enzyme‐activatable optical probes for bioimaging

“…Considering the critical roles of cathepsin B in tumor-associated processes, a series of cathepsin Bactivatable probes have been recently reported for bioimaging or theranostics. [120][121][122][123][124] The most recently reported probes 35 and 36 are depicted in Figure 17 to elucidate the design principle, working mechanism, and performance of cathepsin Bactivatable probes.…”