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

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-infra...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2018-10, Vol.90 (19), p.11629-11635
Main Authors: Xie, Xilei, Tang, Fuyan, Liu, Guangzhao, Li, Yong, Su, Xingxing, Jiao, Xiaoyun, Wang, Xu, Tang, Bo
Format: Article
Language:English
Subjects:
Animal models
Anthracycline
Biomarkers
Cancer therapies
Cardiomyocytes
Cardiotoxicity
Chemistry
Fluorescent indicators
I.R. radiation
Infrared radiation
Mitochondria
Mitochondrial DNA
Peroxynitrite
Toxicology
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Summary: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.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.8b03207