Hypochlorous acid-activated two-photon fluorescent probe for evaluation of anticancer drug-induced cardiotoxicity and screening of antioxidant drugs

Abstract

While the widespread use of chemotherapy has greatly improved the survival rates of cancer patients, this has been accompanied by immense suffering derived from significant toxic side effects. Since the cardiotoxicity caused by anticancer drugs seriously affects the prognosis and life quality of cancer patients, it is crucial to monitor the early stage of cardiotoxicity and myocardial damage induced by chemotherapy drugs in a timely manner. However, the traditional diagnostic methods have several disadvantages, including lack of specificity and delayed detection. Herein we developed a lysosomal targeted two-photon fluorescent probe (THPIC) for the real-time tracking of endogenous HClO specifically. THPIC has been employed as an imaging and diagnostic tool to verify that the administration of different anticancer drugs could lead to the elevation of HClO at varying degrees in H9C2 cells and the corresponding heart tissue sections, which would be prevented by the pre-treatment of conventional antioxidant drugs. Moreover, the results of H&E staining and western blot assay showed that the up-regulated HClO induced the activation of TNF-α through oxidative stress and then caused cardiotoxicity and myocardial injury. Antioxidant drugs canprotect the heart by depleting elevated ROS to maintain a normal redox balance in H9C2 cells. Therefore, HClO can be regarded as a biomarker for evaluating cardiotoxicity induced by anticancer drugs, and THPIC can be applied as a platform for screening drugs to prevent cardiotoxicity.