期刊
ANALYTICAL CHEMISTRY
卷 90, 期 19, 页码 11629-11635出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.8b03207
关键词
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资金
- National Natural Science Foundation of China [21535004, 91753111, 21505088, 21775093, 21390411]
- Key Research and Development Program of Shandong Province [2018YFJH0502]
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.
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