Development of mitochondria-immobilized polarity/viscosity-responsive near-infrared (NIR)-emissive fluorescent probes for the ferroptosis-associated drug screening

Exploration of new ferroptosis-associated drugs can provide creationary cytoprotective approaches and innovative therapeutic methods for the formerly incurable diseases. Herein, we present a strategy for the ferroptosis-associated drug screening by employing mitochondria-immobilized NIR-emissive fluorescent probes (DCP and BCV). Bioimaging results validated DCP and BCV possessed brilliant mitochondria-immobilized capacity, and erastin-induced ferroptosis observably increases mitochondrial polarity/viscosity. Quercetin was esterified to provide various derivatives with higher partition coefficients (logP). By using mitochondrial polarity/viscosity as indicators, the acetylated quercetin was screened as a potent drug to inhibit ferroptosis. Aided by optical tests and HPLC analysis, the inhibition mechanism of acetylated quercetin to ferroptosis was speculated to base on the integration of the Fe(II)-chelating effect and antioxidative activity of quercetin. Collectively, this work demonstrated that fluorescence imaging of mitochondrial polarity/viscosity can afford a convenient and tangible strategy to screen new ferroptosis-associated drugs.