RNA-cleaving
DNAzymes have emerged as a promising tool for metal
ion detection. Achieving spatiotemporal control over their catalytic
activity is essential for understanding the role of metal ions in
various biological processes. While photochemical and endogenous stimuli-responsive
approaches have shown potential for controlled metal ion imaging using
DNAzymes, limitations such as photocytotoxicity, poor tissue penetration,
or off-target activation have hindered their application for safe
and precise detection of metal ions in vivo. We herein
report a chemically inducible DNAzyme in which the catalytic core
is modified to contain chemical caging groups at the selected backbone
sites through systematic screening. This inducible DNAzyme exhibits
minimal leakage of catalytic activity and can be reactivated by small
molecule selenocysteines, which effectively remove the caging groups
and restore the activity of DNAzyme. Benefiting from these findings,
we designed a fluorogenic chemically inducible DNAzyme sensor for
controlled imaging of metal ions with tunable activity and high selectivity
in live cells and in vivo. This chemically inducible
DNAzyme design expands the toolbox for controlling DNAzyme activity
and can be easily adapted to detect other metal ions in vivo by changing the DNAzyme module, offering opportunities for precise
biomedical diagnosis.