Unimolecular Chemo-fluoro-luminescent Reporter for Crosstalk-Free Duplex Imaging of Hepatotoxicity
Unimolecular Chemo-fluoro-luminescent Reporter for Crosstalk-Free Duplex Imaging of Hepatotoxicity
复制标题
DOI：
10.1021/jacs.9b02580
复制
发表时间：
2019-07-10
影响因子：
15
通讯作者：
Pu, Kanyi
中科院分区：
文献类型：
--
作者：
Cheng, Penghui;Miao, Qingqing;Pu, Kanyi
实时多重成像对于生物学和诊断至关重要，但对于光学模态仍然具有挑战性。在此，合成了一种单分子化学荧光发光报告基因（CFR），用于药物引起的肝毒性（DIH）的双重成像，这是一个长期的医学问题。 CFR通过分别激活其独立的化学发光和近红外荧光通道，同时检测超氧阴离子（O-2（中心点））和caspase-3（casp3）。 CFR 的这种无串扰双工成像功能能够纵向测量 DIH 进展过程中的两个相关生物分子事件（氧化应激和细胞凋亡），将 O-2（中心点）确定为体外和体内检测 DIH 的早期生物标志物。此外，CFR 比组织学变化早 17.5 小时检测到 DIH。因此，我们的研究不仅开发了一种用于早期检测 DIH 的灵敏光学报告基因，而且还为双重成像提供了通用的分子设计策略。
Real-time multiplex imaging is imperative to biology and diagnosis but remains challenging for optical modality. Herein, a unimolecular chemo-fluoro-luminescent reporter (CFR) is synthesized for duplex imaging of drug-induced hepatotoxicity (DIH), a long-term medical concern. CFR simultaneously detects superoxide anion (O-2(center dot)) and caspase-3 (casp3) through respective activation of its independent chemiluminescence and near-infrared fluorescence channels. Such a crosstalk-free duplex imaging capability of CFR enables longitudinal measurement of two correlated biomolecular events (oxidative stress and cellular apoptosis) during the progression of DIH, identifying O-2(center dot) as an earlier biomarker for detection of DIH both in vitro and in vivo. Moreover, CFR detects DIH 17.5 h earlier than histological changes. Thus, our study not only develops a sensitive optical reporter for early detection of DIH but also provides a general molecular design strategy for duplex imaging.