Development of Dual-Responsive Fluorescent Probe for Drug Screening of Diabetes Cardiomyopathy

Abstract

For specific drug research and development, a drug-screening strategy (DSS) plays an indispensable role in the biomedical field. Unfortunately, traditional strategies are complicated and insufficiently accurate due to the widely used single-target screening method. Herein, a simple dual-target-based drug-screening strategy (dt-DSS) is proposed to screen highly effective drugs by fluorescence imaging. As a proof of concept, we utilized a dual-responsive fluorescence probe to screen drugs for diabetic cardiomyopathy (DCM). We first developed and took advantage of a dual-response probe HDB to detect reactive oxygen species (ROS) and mitophagy levels in cellular starvation and high glucose models. Based on this, HDB was utilized to study the effects of different drugs in the mitophagy process caused by the high-glucose cell model for DCM. Combined with Western blotting assays, we found that Drp-1 inhibitors could fundamentally reduce mitophagy caused by the high-glucose cells model. Compared with commercial single-target antioxidant drugs, the drugs with simultaneous antioxidant capacity and Drp-1 inhibition screened by dt-DSS, such as resveratrol and icariin, could treat DCM better. Therefore, HDB as an effective tool could accurately and quickly screen high-potency drugs for DCM. We believe that this work provides an attractive strategy to explore the pathogenesis of diabetic cardiomyopathy and precisely screen for highly effective drugs.