Simultaneous Detection of Mitochondrial Hydrogen Selenide and Superoxide Anion in HepG2 Cells under Hypoxic...

Previous studies proposed that sodium selenite (Na₂SeO₃) was reduced to hydrogen selenide (H₂Se) and that H₂Se subsequently reacted with oxygen to generate superoxide anion (O₂^•-), resulting in tumor cell oxidative stress and apoptosis. However, under the hypoxic conditions of a solid tumor, the anticancer mechanism of sodium selenite remains unclear. To reveal the exact anticancer mechanism of selenite in the real tumor microenvironment, we developed a mitochondria-targeting fluorescent nanosensor, Mito-N-D-MSN, which was fabricated from mesoporous silica nanoparticles (MSNs) loaded with two small-molecule fluorescent probes and a triphenylphosphonium ion as a mitochondria-targeting moiety. With Mito-N-D-MSN, the fluctuations in the contents of mitochondrial hydrogen selenide (H₂Se) and superoxide anion (O₂^•-) in HepG2 cells induced by Na₂SeO₃ were investigated in detail under normoxic and hypoxic conditions. The results showed that the mitochondrial H₂Se content increased gradually, while the O₂^•- content remained unchanged in HepG2 cells under hypoxic conditions, which indicated that the anticancer mechanism of selenite involves nonoxidative stress in the real tumor microenvironment.