Activatable chemiluminescent
probes that show enhanced chemiluminescence
upon interaction with a molecular target of interest have offered
promising tools for sensing and bioimaging in terms of low background,
high sensitivity, and improved penetration depth in biological tissues.
Here, we reported a γ-glutamyl transpeptidase (GGT) activatable
chemiluminescent probe for real-time detection of GGT activity in
vitro and in living mice. The probe was designed by caging an electron-withdrawing
acrylic group-substituted Schaap’s phenoxy-dioxetane with a
GGT-recognitive substrate (γ-Glu) and a self-immolative linker
(p-aminobenzyl alcohol), which was initially chemiluminescence
off. Upon interaction with GGT, strong chemiluminescence with a more
than 800-fold turn-on ratio could be achieved in aqueous solution,
allowing to specifically detect GGT activity with ultrahigh signal-to-background
ratio and sensitivity in vitro and in live cells. We demonstrated
that the probe was reliable to quantify the GGT in serum, permitting
to accurately report the elevated levels of GGT in lipopolysaccharide-treated
mouse serum. Moreover, through real-time chemiluminescence imaging
of GGT activity, the designed probe was feasible to detect GGT-positive
tumors in living mice after intravenous systemic administration. This
study demonstrates the high potential of GGT-activatable chemiluminescent
probe for serum assays and molecular imaging, which might find wide
applications in diagnosis of GGT-related diseases.