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Mitochondrial Peroxynitrite Mediation of Anthracycline-Induced Cardiotoxicity as Visualized by a Two-Photon Near-Infrared Fluorescent Probe
- Xie, Xilei, Tang, Fuyan, Liu, Guangzhao, Li, Yong, Su, Xingxing, Jiao, Xiaoyun, Wang, Xu, Tang, Bo
- Analytical chemistry 2018 v.90 no.19 pp. 11629-11635
- animal models, anthracyclines, biomarkers, cardiomyocytes, cardiotoxicity, drugs, fluorescent dyes, image analysis, mitochondria
- 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.