Dual-responsive fluorescent probe for imaging NAD(P)H and mitochondrial viscosity and its application in cancer cell ferroptosis

Herein, we design and synthesize a dual-responsive fluorescent probe 3Q-2 and use it to reveal the dynamic changes of NAD(P)H and mitochondrial viscosity during ferroptosis, a newly discovered form of cell death. 3Q-2 displays two separate spectra when responding to NAD(P)H and mitochondrial viscosity, respectively, with high sensitivity, selectivity, and no cross-interference. We find that cancer cells possess distinct levels of NAD(P)H and mitochondrial viscosity during ferroptosis induced by cystine transporter SLC7A11 inhibitor erastin and glutathione peroxidase 4 (GPX4) inhibitor RSL4, respectively. As a robust method simultaneously detecting NAD(P)H and mitochondrial viscosity, 3Q-2 may be expected to find more applications in other physiological and pathological scenarios.