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生物硫醇激活的近红外上转换发光探针用于早期评估药物诱导的肝毒性。

Biothiols-activated near-infrared frequency up-conversion luminescence probe for early evaluation of drug-induced hepatotoxicity.

机构信息

Key Laboratory of Organo-Pharmaceutical Chemistry of Jiangxi Province, School of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou, 341000, PR China.

School of Engineering, China Pharmaceutical University, Nanjing, 211198, PR China.

出版信息

Anal Chim Acta. 2024 Jul 11;1312:342768. doi: 10.1016/j.aca.2024.342768. Epub 2024 May 21.

DOI:10.1016/j.aca.2024.342768
PMID:38834271
Abstract

A novel biothiols-sensitive near-infrared (NIR) fluorescent probe RhDN based on a rhodamine skeleton was developed for early detection of drug-induced hepatotoxicity in living mice. RhDN can be used not only as a conventional large stokes shift fluorescent (FL) probe, but also as a kind of anti-Stokes frequency upconversion luminescence (FUCL) molecular probe, which represents a long wavelength excitation (808 nm) to short wavelength emission (760 nm), and response to Cys/Hcy/GSH with high sensitivity. Compared with traditional FL methods, the FUCL method exhibited a lower detection limit of Cys, Hcy, and GSH in 75.1 nM, 101.8 nM, and 84.9 nM, respectively. We exemplify RhDN for tracking endogenously biothiols distribution in living cells and further realize real-time in vivo bioimaging of biothiols activity in mice with dual-mode luminescence system. Moreover, RhDN has been successfully applied to visualize the detection of drug-induced hepatotoxicity in living mice. Overall, this report presents a unique approach to the development of large stokes shift NIR FUCL molecular probes for in vitro and in vivo biothiols biosensing.

摘要

一种基于罗丹明骨架的新型生物硫醇敏感近红外(NIR)荧光探针 RhDN 被开发用于活鼠体内药物诱导肝毒性的早期检测。RhDN 不仅可以用作常规大斯托克斯位移荧光(FL)探针,还可以用作一种反斯托克斯频移上转换发光(FUCL)分子探针,其代表长波长激发(808nm)到短波长发射(760nm),并对 Cys/Hcy/GSH 具有高灵敏度的响应。与传统的 FL 方法相比,FUCL 方法对 Cys、Hcy 和 GSH 的检测限分别为 75.1 nM、101.8 nM 和 84.9 nM。我们举例说明了 RhDN 在跟踪活细胞内内源性生物硫醇分布方面的应用,并进一步通过双模式发光系统实现了对小鼠体内生物硫醇活性的实时体内生物成像。此外,RhDN 已成功应用于可视化检测活鼠体内药物诱导的肝毒性。总的来说,本报告提出了一种独特的方法来开发用于体外和体内生物硫醇生物传感的大斯托克斯位移 NIR FUCL 分子探针。

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Precision Imaging of Biothiols in Live Cells and Treatment Evaluation during the Development of Liver Injury via a Near-Infrared Fluorescent Probe.通过近红外荧光探针实现活细胞中生物硫醇的精准成像及肝损伤发展过程中的治疗评估
Chem Biomed Imaging. 2024 Aug 28;3(3):169-179. doi: 10.1021/cbmi.4c00048. eCollection 2025 Mar 24.