<br>一氧化碳：与粘度结合的第二种生物标记物，用于构建“双锁”近红外荧光探针，以准确诊断非酒精性脂肪肝,Analytical Chemistry

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一氧化碳：与粘度结合的第二种生物标记物，用于构建“双锁”近红外荧光探针，以准确诊断非酒精性脂肪肝
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-12-06 , DOI: 10.1021/acs.analchem.3c04676
Shaohui Han ₁ , Yuyang Zeng ₁ , Yiling Li ₁ , Haipu Li ₁ , Lei Yang ₂ , Xiaojie Ren _{1,

3} , Minhuan Lan ₁ , Benhua Wang ₁ , Xiangzhi Song ₁

Affiliation

如果不及时治疗，非酒精性脂肪肝（NAFLD）可能会发展为肝硬化和肝癌。因此，开发有用的工具来无创、准确地诊断 NAFLD 具有重要意义。微环境粘度增加被认为是NAFLD的生物标志物，但其他肝脏疾病中粘度增加的发生极大地降低了单次粘度检测诊断NAFLD的准确性。因此，寻找NAFLD的第二个生物标志物非常有必要。创新性地提出，NAFLD 中过度表达的血红素加氧酶 1 酶会在肝细胞中产生异常高浓度的 CO，CO 可以作为潜在的生物标志物。在这项工作中，我们筛选了九种结构精致的内酰胺长沙染料（ HCO-1 – HCO-9 ），以获得近红外（NIR）、无金属、“双锁”荧光探针，用于同时检测CO和粘度。带有2-吡啶基腙取代基的长沙染料可以感应CO，并且2-吡啶基部分上的5位取代基对反应速率有很大的电子效应。这些染料中的双键充当粘度传感基团。探针HCO-9通过同时检测CO和粘度来精确诊断NAFLD。在高粘度微环境中与 CO 反应后，探针HCO-9在 745 nm 处的强荧光在 700 nm 处的 NIR 激发下打开。探头HCO-9被证明是 CO 和粘度成像的有效工具。由于具有近红外吸收和低毒性的优点，探针HCO-9成功应用于小鼠模型NAFLD的成像。

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Carbon Monoxide: A Second Biomarker to Couple with Viscosity for the Construction of “Dual-Locked” Near-Infrared Fluorescent Probes for Accurately Diagnosing Non-Alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) can progress to cirrhosis and liver cancer if left untreated. Therefore, it is of great importance to develop useful tools for the noninvasive and accurate diagnosis of NAFLD. Increased microenvironmental viscosity was considered as a biomarker of NAFLD, but the occurrence of increased viscosity in other liver diseases highly reduces the diagnosis accuracy of NAFLD by a single detection of viscosity. Hence, it is very necessary to seek a second biomarker of NAFLD. It has been innovatively proposed that the overexpressed heme oxygenase-1 enzyme in NAFLD would produce abnormally high concentrations of CO in hepatocytes and that CO could serve as a potential biomarker. In this work, we screened nine lactam Changsha dyes (HCO-1–HCO-9) with delicate structures to obtain near-infrared (NIR), metal-free, and “dual-locked” fluorescent probes for the simultaneous detection of CO and viscosity. Changsha dyes with a 2-pyridinyl hydrazone substituent could sense CO, and the 5-position substituents on the 2-pyridinyl moiety had a great electron effect on the reaction rate. The double bond in these dyes served as the sensing group for viscosity. Probe HCO-9 was utilized for precise diagnosis of NAFLD by simultaneous detection of CO and viscosity. Upon reacting with CO in a high-viscosity microenvironment, strong fluorescence at 745 nm of probe HCO-9 was turned on with NIR excitation at 700 nm. Probe HCO-9 was proven to be an effective tool for imaging CO and viscosity. Due to the advantages of NIR absorption and low toxicity, probe HCO-9 was successfully applied to image NAFLD in a mouse model.

更新日期：2023-12-06

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