Hypochlorous acid-activated two-photon fluorescent probe for evaluation of anticancer drug-induced cardiotoxicity and screening of antioxidant drugs
Hypochlorous acid-activated two-photon fluorescent probe for evaluation of anticancer drug-induced cardiotoxicity and screening of antioxidant drugs
复制标题
次氯酸激活双光子荧光探针评价抗癌药物引起的心脏毒性及筛选抗氧化药物
DOI：
10.1039/d2qo01408d
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发表时间：
2022-10-04
影响因子：
5.4
通讯作者：
Tang，Bo
中科院分区：
文献类型：
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作者：
Liu，Kaiqiang;Zhang，Jian;Tang，Bo
虽然化疗的广泛使用大大提高了癌症患者的存活率，但伴随而来的是巨大的毒副作用带来的痛苦。由于抗癌药物引起的心脏毒性严重影响癌症患者的预后和生活质量，因此及时监测化疗药物引起的心脏毒性和心肌损害的早期情况至关重要。然而，传统的诊断方法存在特异性不足、检测滞后等缺点。在此，我们开发了一种溶酶体靶向双光子荧光探针（THPIC），用于特异性实时跟踪内源性HClO。THPIC被用作成像和诊断工具，以验证不同抗癌药物的使用可导致H9C2细胞和相应心脏组织切片中不同程度的HClO升高，而这是常规抗氧化药物预处理无法阻止的。H&E染色和western blot结果显示，上调的HClO通过氧化应激诱导TNF-α活化，引起心肌毒性和心肌损伤。抗氧化药物可以通过消耗升高的ROS来保护心脏，维持H9C2细胞正常的氧化还原平衡。因此，HClO可作为评价抗癌药物心脏毒性的生物标志物，THPIC可作为筛选预防心脏毒性药物的平台。
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.