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用于连续检测内源性 ONOO 和线粒体粘度的多功能传感器:区分正常和癌症模型。

Multifunctional Sensors for Successive Detection of Endogenous ONOO and Mitochondrial Viscosity: Discriminating Normal to Cancer Models.

机构信息

Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, and School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China.

Department of Chemistry Education, Daegu University, Daegudae-ro 201, Gyeongsan-si, Gyeongsangbuk-do 38453, Republic of Korea.

出版信息

Anal Chem. 2024 Oct 15;96(41):16289-16297. doi: 10.1021/acs.analchem.4c03245. Epub 2024 Sep 30.

Abstract

Diagnosing cancer in its early stages can play an important role in prolonging the lifespan of patients, which demands the use of powerful tools to detect biomarkers accurately. However, since most fluorescent probes described for cancer diagnosis are limited to recognizing a single molecule, achieving the high accuracy criteria remains difficult. Here, sensor is constructed for the sequential detection of , ONOO, and viscosity. Initially, sensor detected and underwent an intramolecular charge transfer mechanism, resulting in the formation of and fluorescence quenching at 587 nm. Subsequently, the intermediate () monitored ONOO and reproduced sensor reversibly with fluorescence enhancement at 496 nm, showing concentration-related quantitative analysis. Similar sensing processes were observed in monitoring ONOO and viscosity by synthetically developed sensor . The proposed mechanisms of sensors and are verified through various characterizations (H NMR, HR-MS, and HPLC) and DFT calculations. Investigations on endogenous ONOO and mitochondrial viscosity in cancer (HeLa) and normal (NCM460) cells were conducted to distinguish cancerous cells from normal cells. We anticipated that sensor could effectively serve as a reliable bioanalytical reagent for cancer diagnosis at an earlier stage through sequential detection of two cancer markers, ONOO and mitochondrial viscosity, in living cells. Importantly, sensor has been employed for imaging ONOO in normal and liver injury mouse models and tissues, achieving outstanding results.

摘要

在早期诊断癌症可以在延长患者的寿命方面发挥重要作用,这需要使用强大的工具来准确检测生物标志物。然而,由于大多数用于癌症诊断的荧光探针仅限于识别单个分子,因此达到高精度标准仍然很困难。在这里,构建了用于顺序检测 、ONOO 和粘度的传感器。最初,传感器 检测 和经历分子内电荷转移机制,导致 和荧光猝灭在 587nm。随后,中间体()监测 ONOO 并通过荧光增强在 496nm 处可逆地再现传感器 ,显示出与浓度相关的定量分析。通过各种表征(H NMR、HR-MS 和 HPLC)和 DFT 计算验证了传感器 和 的传感机制。在癌症(HeLa)和正常(NCM460)细胞中进行了内源性 ONOO 和线粒体粘度的研究,以区分癌细胞和正常细胞。我们预计,传感器 通过在活细胞中顺序检测两种癌症标志物(ONOO 和线粒体粘度),可以有效地用作癌症早期诊断的可靠生物分析试剂。重要的是,传感器 已经用于正常和肝损伤小鼠模型和组织中 ONOO 的成像,取得了优异的结果。

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