Cycling hypoxia has been recognized as a typical characteristic of a wide range of hepatic diseases, and its real time imaging is of necessity for better understanding of its biological functions. However, effective optical probes for reversible hypoxia detection in liver are lacking. Herein, we designed a near-infrared fluorescence/photoacoustic (NIRF/PA) probe, AzoCys-CF₃, that displayed a highly selective and reversible off-on switching of both NIRF and PA signals in response to normoxia-hypoxia cycles. AzoCys-CF₃ could not only monitor the acute hypoxia status during the hepatic ischemia-reperfusion process, but also track the extent of chronic hepatic hypoxia in NAFLD model mice. Antioxidant drug screening by AzoCys-CF₃ demonstrated that the hepatoprotective drug orlistat significantly attenuated hypoxia in the livers of NAFLD mice. This work provided a reliable NIRF/PA imaging agent for in vivo monitoring of cycling hypoxia, showing potential application in screening drugs for hepatic diseases.

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中文翻译：

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急慢性肝损伤缺氧状态的双模式可逆成像

循环缺氧已被认为是多种肝脏疾病的典型特征，其实时成像对于更好地了解其生物学功能是必要的。然而，缺乏用于检测肝脏可逆缺氧的有效光学探针。在这里，我们设计了一种近红外荧光/光声（NIRF/PA）探针， 偶氮半胱氨酸-CF ₃，其显示出响应常氧-缺氧循环的 NIRF 和 PA 信号的高度选择性和可逆的开关。 偶氮半胱氨酸-CF ₃不仅可以监测肝脏缺血再灌注过程中的急性缺氧状态，还可以追踪NAFLD模型小鼠慢性肝脏缺氧的程度。抗氧化药物筛选 偶氮半胱氨酸-CF ₃证明保肝药物奥利司他显着减轻 NAFLD 小鼠肝脏缺氧。这项工作为循环缺氧的体内监测提供了可靠的 NIRF/PA 成像剂，显示出在筛选肝病药物方面的潜在应用。

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