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用于体内检测 ONOO- 相关肝毒性的生色团修饰的高选择性比率上转换纳米探针。

Chromophore-Modified Highly Selective Ratiometric Upconversion Nanoprobes for Detection of ONOO -Related Hepatotoxicity In Vivo.

机构信息

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China.

State Key Laboratory of Natural Medicines, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 211198, China.

出版信息

Small. 2019 Oct;15(43):e1902737. doi: 10.1002/smll.201902737. Epub 2019 Sep 4.

Abstract

Acute hepatitis is a major problem affecting public health and has attracted more and more attention. Generally, as the standard means, blood tests are taken for evaluating hepatitis. However, such tests fail to accurately reflect the level of hepatitis in vivo. Herein, two highly selective ratiometric fluorescent probes are designed to track peroxynitrite (ONOO ) as the hepatitis indicator, and further evaluate acute liver injury in vivo through dye-grafted upconversion nanoparticles (UCNPs). Specifically, upconversion luminescence of nanoprobes at 540 or 660 nm can be quenched by the designed and synthesized chromophore E-CC or H-CC, that can be destroyed by ONOO via energy transfer (ET) process, while the upconversion luminescence intensity at 810 nm remains the same. Thus, the developed nanoprobes can be used for ratiometric detection (I /I or I /I ) of ONOO . Moreover, the developed near infrared ratiometric nanoprobes can highly selectively detect ONOO , which can eliminate the interference of HOCl and SO . Finally, it is demonstrated that this highly selective ratiometric nanosystem can achieve effective detection of ONOO in living cells and CCl -induced acute liver injury models. It provides some reference value for clinical detection of hepatotoxicity.

摘要

急性肝炎是影响公众健康的一个主要问题,已引起越来越多的关注。一般来说,作为标准手段,通过血液检测来评估肝炎。然而,这些检测方法无法准确反映体内肝炎的水平。在这里,我们设计了两种高选择性的比率荧光探针来跟踪过氧亚硝酸盐(ONOO-)作为肝炎标志物,并通过染料接枝上转换纳米粒子(UCNPs)进一步在体内评估急性肝损伤。具体来说,纳米探针在 540nm 或 660nm 的上转换发光可以被设计和合成的生色团 E-CC 或 H-CC 猝灭,ONOO-可以通过能量转移(ET)过程破坏它们,而在 810nm 的上转换发光强度保持不变。因此,所开发的纳米探针可用于 ONOO-的比率检测(I/I 或 I/I)。此外,所开发的近红外比率纳米探针可以高选择性地检测 ONOO-,可以消除 HOCl 和 SO2-的干扰。最后,证明这种高选择性的比率纳米系统可以在活细胞和 CCl4-诱导的急性肝损伤模型中实现对 ONOO-的有效检测。它为临床检测肝毒性提供了一些参考价值。

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