The accurate diagnosis of Drug-induced liver injury (DILI) plays essential role for the effective treatment and avoiding the worsening of liver injury. Considering superoxide anion (O₂^•-) is closely associated with the progression of DILI, molecular probes that achieve high-contrast photoacoustic (PA) imaging of O₂^•- in deeper tissues with high spatial resolution are valuable tools for the accurate diagnosis of DILI. However, the existing PA probes for O₂^•- display the relatively short absorption wavelength and small bathochromic shift, limiting their PA activation folds. Here we construct a new O₂^•- activatable 7-Azaindole derived probe (AIH-OTF) for PA imaging of DILI in vivo. A novel 7-Azaindole modified hemicyanine dye (AIH-OH) is incorporated as the PA reporter of AIH-OTF due to its long absorption wavelength, large molar extinction cofficient and low fluorescence quantum yield. It is demonstrated that AIH-OTF exhibits the highly sensitive and selective PA response to O₂^•- with a large bathochromic shift (203 nm) and high activation fold (9.7 times). Cellular studies indicate that AIH-OTF can realize high-contrast PA imaging of the dynamic changes of endogenous O₂^•- in living cells. AIH-OTF is successfully applied to detect the occurrence of drug-induced liver injury and assess the therapeutic efficacy through its PA response to O₂^•-. We expect that AIH-OTF may serve as a useful imaging tool for the diagnosis and pathogenesis research of DILI.

中文翻译：

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一种超氧阴离子可激活的 7-氮杂吲哚衍生的光声探针，用于药物性肝损伤的高对比度成像


药物性肝损伤 （DILI） 的准确诊断对于肝损伤的有效治疗和避免肝损伤恶化起着至关重要的作用。考虑到超氧阴离子 （O₂^•-） 与 DILI 的进展密切相关，在更深组织中实现 O₂^•- 的高空间分辨率高对比度光声 （PA） 成像的分子探针是准确诊断 DILI 的宝贵工具。然而，现有的 O₂^•- PA 探针显示出相对较短的吸收波长和小的深褐色偏移，限制了它们的 PA 激活折叠。在这里，我们构建了一种新的 O₂^•- 可激活的 7-氮杂吲哚衍生探针 （AIH-OTF），用于体内 DILI 的 PA 成像。一种新的 7-氮杂吲哚 修饰的半菁染料 （AIH-OH） 因其吸收波长长、摩尔消光率大和荧光量子产率低而被掺入作为 AIH-OTF 的 PA 报告基因。结果表明，AIH-OTF 对 O₂^•- 表现出高度敏感和选择性的 PA 反应，具有大的深变色偏移 （203 nm） 和高活化倍数 （9.7 倍）。细胞研究表明，AIH-OTF 可以实现活细胞中内源性 O₂^•- 动态变化的高对比度 PA 成像。AIH-OTF 已成功应用于检测药物性肝损伤的发生，并通过其 PA 对 O₂^•- 的反应评估治疗效果。我们期望 AIH-OTF 可作为 DILI 诊断和发病机制研究的有用成像工具。