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一种新型高选择性的以新型查尔酮荧光团为荧光探针,用于监测和成像活细胞和药物损伤的肝组织内源性过氧亚硝酸盐。

A novel highly selective fluorescent probe with new chalcone fluorophore for monitoring and imaging endogenous peroxynitrite in living cells and drug-damaged liver tissue.

机构信息

School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.

Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 210009, China.

出版信息

Talanta. 2020 Aug 1;215:120934. doi: 10.1016/j.talanta.2020.120934. Epub 2020 Mar 14.

Abstract

As a member of the reactive nitrogen species (RNS) family, peroxynitrite (ONOO) as an oxidant and nitrating mediator plays a significant role in some physiopathologic processes. The excessive production of peroxynitrite anion in a drug-damaged liver is a culprit of hepatotoxicity. The detection of peroxynitrite is of vital importance for the treatment of some diseases including cancer and liver injury. In this study, a novel turn-on fluorescent probe IC-ONOO with new chalcone fluorophore was designed and synthesized for the detection of in vitro and in vivo. The probe responded rapidly towards ONOO (only within 15 min did the fluorescent intensity maximize), and was endowed with high sensitivity and excellent selectivity. Given the fact that the linear correlation between the fluorescent intensity at 560 nm and the concentrations of the probe ranged from 0 to 9 μM, the limit of detection (LOD) was calculated to be 3.1 × 10 M. With all the merits, probe IC-ONOO was qualified as a robust tool to monitor peroxynitrite anion under physiopathologic condition. Moreover, it was successfully applied in the imaging of endogenous peroxynitrite in living MCF-7 cells (Human breast carcinoma cells) and mouse drug-damaged liver tissue with low cytotoxicity. Given all the extraordinary merits, great potential has been seen in its application to other peroxynitrite related diseases.

摘要

作为活性氮物种 (RNS) 家族的一员,过氧亚硝酸盐 (ONOO) 作为氧化剂和硝化介质,在一些生理病理过程中发挥着重要作用。药物损伤的肝脏中过氧亚硝酸盐阴离子的过度产生是肝毒性的罪魁祸首。过氧亚硝酸盐的检测对于包括癌症和肝损伤在内的一些疾病的治疗至关重要。在这项研究中,设计并合成了一种具有新型查尔酮荧光团的新型 ON00 荧光探针 IC-ONOO,用于体外和体内检测。探针对 ONOO 反应迅速(仅在 15 分钟内荧光强度达到最大值),具有高灵敏度和出色的选择性。鉴于 560nm 处荧光强度与探针浓度之间的线性关系范围从 0 到 9μM,检测限 (LOD) 计算为 3.1×10 -6 M。由于所有这些优点,探针 IC-ONOO 被证明是监测生理病理条件下过氧亚硝酸盐阴离子的有力工具。此外,它还成功地应用于活 MCF-7 细胞(人乳腺癌细胞)和小鼠药物损伤肝组织内源性过氧亚硝酸盐的成像,具有低细胞毒性。鉴于所有这些卓越的优点,它在其他与过氧亚硝酸盐相关的疾病中的应用具有很大的潜力。

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