Red-emitting aggregation-induced emission fluorescent probe for monitoring fluctuation of HClO in mitochondria during ferroptosis.

Background: Ferroptosis is an iron-dependent programmed cell death pathway driven by lipid peroxidation that involves various inflammation-related diseases and even cancer, which is often accompanied by the accumulation of mitochondrial ROS. HClO, as one of the vital ROS in organisms, is mainly derived from the mitochondria of cells. And abnormal levels of HClO can disrupt redox homeostasis in cells and lead to various diseases. Importantly, intracellular HClO levels are also associated with ferroptosis. Therefore, it is very important to study the fluctuation of intracellular HClO level during ferroptosis.

Results: Herein, a HClO fluorescent probe TPA-ClO was synthesized using triphenylamine fluorophore and benzothiadiazole structure. Notably, TPA-ClO exhibited the advantages of NIR fluorescence emission, good AIE properties and large Stokes shift, and which could selectively detect HClO with a detection limit of 150.0 nM. TPA-ClO could be well targeted in mitochondria and had been successfully applied to monitor exogenous and endogenous HClO in MCF7 cells. Moreover, the imaging experiment of TPA-ClO indicated that erastin- and RSL3-induced ferroptosis in MCF7 cells led to increased levels of mitochondrial HClO and that MCF7 cells showed high ferroptosis sensitivity to RSL3.

Conclusions: TPA-ClO exhibited high selectivity to HClO over other potential interfering substances, and could be employed to monitor HClO level fluctuations in MCF7 cells. More importantly, TPA-ClO could be an effective tool to monitor the fluctuations of HClO level in mitochondria during ferroptosis as well as for investigating various diseases associated with ferroptosis for future research.