Mitochondrial Peroxynitrite Mediation of Anthracycline-Induced Cardiotoxicity as Visualized by a Two-Photon Near-Infrared Fluorescent Probe

作者：Xie, Xilei^*; Tang, Fuyan; Liu, Guangzhao; Li, Yong; Su, Xingxing; Jiao, Xiaoyun; Wang, Xu^*; Tang, Bo^*

来源：Analytical Chemistry, 2018, 90(19): 11629-11635.

DOI：10.1021/acs.analchem.8b03207

• AGGREGATION-INDUCED EMISSION
• DRUG-INDUCED HEPATOTOXICITY
• IN-VIVO
• NITRIC-OXIDE
• LIVE CELLS
• ENDOGENOUS PEROXYNITRITE
• BIOLOGICAL APPLICATIONS
• ANTICANCER TREATMENTS
• SELECTIVE DETECTION
• HYDROGEN-PEROXIDE

Anthracyclines rank among the most efficacious anticancer medications. However, their clinical utility and oncologic efficacy are severely compromised by the cardiotoxicity risk facing the early-diagnosis difficulty and their unclear molecular mechanism. Herein, a two-photon-excitable and near-infrared-emissive fluorescent probe, TPNIR-FP, was fabricated and endowed with extraordinary specificity and sensitivity and a rapid response toward peroxynitrite (ONOO-), as well as mitochondria-targeting ability. With the aid of TPNIR-FP, we demonstrate that mitochondrial ONOO- is upregulated in the early stage and contributes to the onset and progression of anthracycline cardiotoxicity in cardiomyocyte and mouse models; therefore, it represents an early biomarker to predict subclinical cardiotoxicity induced by drug challenge. Furthermore, TPNIR-FP is proved to be a robust imaging tool to provide critical insights into drug-induced cardiotoxicity and other ONOO- related pathophysiological processes.

• 出版日期2018-10-2
• 单位山东师范大学