Monitoring
hypoxia-related changes in subcellular organelles would
provide deeper insights into hypoxia-related metabolic pathways, further
helping us to recognize various diseases on subcellular level. However,
there is still a lack of real-time, in situ, and
controllable means for biosensing in subcellular organelles under
hypoxic conditions. Herein, we report a reductase and light programmatical
gated nanodevice via integrating light-responsive
DNA probes into a hypoxia-responsive metal–organic framework
for spatiotemporally controlled imaging of biomolecules in subcellular
organelles under hypoxic conditions. A small-molecule-decorated strategy
was applied to endow the nanodevice with the ability to target subcellular
organelles. Dynamic changes of mitochondrial adenosine triphosphate
under hypoxic conditions were chosen as a model physiological process.
The assay was validated in living cells and tumor tissue slices obtained
from mice models. Due to the highly integrated, easily accessible,
and available for living cells and tissues, we envision that the concept
and methodology can be further extended to monitor biomolecules in
other subcellular organelles under hypoxic conditions with a spatiotemporal
controllable approach.