Fabrication of a Dual-Responsive Fluorescence Probe for Monitoring Cardiac Injury and Repairing by a Golgi-Targeting Hydrogen Sulfide Donor.

Abstract

Doxorubicin (Dox) can cause delayed severe myocardial injury by promoting oxidative stress. The Golgi apparatus is involved in the occurrence and development of cardiovascular diseases. In this work, a dual-responsive fluorescent probe GHO, which can detect simultaneously both Golgi superoxide anion (O₂ ^•-) and peroxynitrite anion (ONOO^-) with two distinct emission bands, is developed for investigating the Golgi stress-mediated myocardial injury mechanism. Furthermore, a synthesized hydrogen sulfide (H₂S) donor (GADT) with Golgi apparatus targeting ability is used for intervening the process of Dox-induced cardiac damage, which shows significant antioxidant capacity in the Golgi apparatus with the help of evaluation of the probe GHO. In detail, compound GADT inhibits Golgi apparatus stress by clearing reactive oxygen species (ROS), thus recover the myocardial damage caused by Dox in cardiomyocytes, zebrafish, and mice. Finally, GADT is proven to play an effective therapeutic role by promoting the degradation of the damaged Golgi apparatus into an autophagosome. Therefore, focusing on the Golgi apparatus, development of the small molecule fluorescent probe GHO and the Golgi-targeting H₂S donor GADT provides a novel perspective for the diagnosis and treatment of Dox-induced myocardial injury mechanism.