一种新型ESIPT荧光探针用于诊断和评估铁死亡介导的HK-2细胞损伤

A Novel ESIPT Fluorescent Probe for the Diagnosis and Assessment of Iron-mediated Acute Kidney Injury

目的:急性肾损伤(AKI)由于缺乏早期诊断生物标志物和实时评估的可视化工具,给AKI早期诊断带来了重大挑战。因此,开发用于早期诊断和评估HK-2细胞损伤的新型探针至关重要。方法:基于ESTPT机制,合成了一种以2-(2'-羟基苯基)苯并噻唑(HBT)衍生物为荧光团的新型荧光探针(MEO-NO),用于检测铁死亡介导的HK-2细胞损伤中过氧亚硝基阴离子(ONOO^(-))。结果:当加入ONOO^(-)时,探针MEO-NO表现出明显的荧光变化,显著的斯托克斯位移(130 nm)和快速反应(约45 s),并具有极高的灵敏度(LOD=7.28 nmol/L)以及高选择性。此外,探针MEO-NO能够在细胞中检测ONOO^(-)。重要的是,MEO-NO可以检测索拉非尼诱导的铁死亡和顺铂(CP)诱导的HK-2细胞损伤过程中的ONOO^(-)。结论:在探针MEO-NO的帮助下,我们成功地在细胞模型中可视化并追踪了ONOO^(-)的变化,探针MEO-NO有望用于诊断和评估铁死亡介导的AKI中的ONOO^(-)水平变化。

Objective To develop novel probes for the early diagnosis and assessment of HK-2 cell injury,as the lack of early diagnostic biomarkers and real-time visualization tools poses significant challenges for the early diagnosis of acute kid⁃ney injury(AKI).Methods A novel fluorescent probe(MEO-NO)with 2-(2′-hydroxyphenyl)benzothiazole(HBT)de⁃rivative as the fluorophore was synthesized based on ESIPT for detecting peroxynitrite anion(ONOO^(-))in ferroptosis-medi⁃ated HK-2 cell injury.Results Upon the addition of ONOO^(-),MEO-NO exhibited distinct fluorescence changes,with a pronounced Stokes shift(130 nm)and rapid response(approximately 45 s),along with high sensitivity(LOD=7.28 nmol/L)and selectivity.MEO-NO also detected ONOO^(-)in cells and the changes in ONOO^(-)during sorafenib-induced fer⁃roptosis and cisplatin(CP)-induced HK-2 cell injury.Conclusion With the assistance of MEO-NO,the changes in ONOO^(-)were successfully visualized and tracked in a cellular model,suggesting the potential of MEO-NO for the early di⁃agnosis and assessment of iron-mediated AKI.