A bifunctional mitochondria-targeted iridium(III) complex for nitroreductase detection in living cells and photodynamic therapy of cancer cells.

Nitroreductase (NTR) can efficiently reduce the nitro group of compounds to an amino group using nicotinamide adenine dinucleotide (NADH) as an electron source. Its expression is upregulated under hypoxic conditions, making it a reliable marker for the degree of hypoxia in tumor cells. Herein, we designed and synthesized a dual-functional iridium complex-based fluorescent probe Ir-NO2 that targets mitochondria, specifically recognizes NTR, and serves as an NTR-activatable photosensitizer for photodynamic therapy (PDT) of tumor cells. The probe is capable of detecting both endogenous and exogenous NTR in cells, as well as enabling NTR recognition in zebrafish. Upon NTR detection, the singlet oxygen yield increased from 0.71 to 0.83. Moreover, both the probe and its NTR-recognized strongly fluorescent produce (Ir-OH) function as dual Type I/II PDT photosensitizers.