As a crucial member in
antioxidant regulatory systems,
sulfane sulfur plays essential roles in cytoprotective mechanisms by directly eliminating ROS and altering ROS-mediated redox signaling. Despite the rising interests in
sulfane sulfur, there only a few bio-compatible methods are available for its direct detection. Moreover, most of the existing methods cannot meet the requirements of real-time detection due to the reactive and labile chemical properties of
sulfane sulfur. Therefore, we strive to clarify the mutual relationship between mitochondria
sulfane sulfur and ROS under
hypoxia stress. Herein, we report a near-infrared
fluorescent probe Mito-SeH for the selective imaging of mitochondrial
sulfane sulfur in cells and in vivo under
hypoxia stress. Mito-SeH includes three moieties: a
selenol group (SeH) as the stronger
sulfur-acceptor; a near-infrared azo-
BODIPY fluorophore as the fluorescent modulator; a lipophilic alkyltriphenylphosphonium
cation as the mitochondrial delivery. Mito-SeH exhibits excellent selectivity and sensitivity towards the detection of mitochondria
sulfane sulfur. The
hypoxia response behavior of Mito-SeH is evaluated in monolayer cell and three-dimensional multicellular spheroid to clarify the relationship between
sulfane sulfur and
hypoxia. We confirm that
sulfane sulfur protection mechanism against
hypoxia is to inhibition of caspase-dependent apoptosis through directly scavenging ROS pathway. The probe is also applied to measurement of
sulfane sulfur in ex vivo-dissected organs of hypoxic mouse model, as well as the probe is successfully used for real-time monitoring the changes of
sulfane sulfur and ROS in acute
ischemia mice model. We suggest that
sulfane sulfur may be a novel therapeutic agent for
hypoxia-induced injury.