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一种基于简单 ICT 的用于 HOCl 检测和生物成像应用的荧光探针。

A Simple ICT-Based Fluorescent Probe for HOCl and Bioimaging Applications.

机构信息

School of Pharmacy, Harbin University of Commerce, Harbin 150076, China.

Engineering Research Center on Natural Antineoplastic Drugs, Ministry of Education, Harbin University of Commerce, Harbin 150076, China.

出版信息

Biosensors (Basel). 2023 Jul 18;13(7):744. doi: 10.3390/bios13070744.

Abstract

Over the past few decades, drug-induced liver damage (DILI) has become a serious public health problem due to drug abuse. Among multifarious reactive oxygen species, mounting evidence attests that ClO has been used as a potential biomarker in DILI. In this work, a new "turn-on" fluorescent probe was designed and synthesized by modifying 4'-hydroxybiphenyl-4-carbonitrile (dye ) with -dimethylthiocarbamate as a response site for detecting ClO. Probe displayed a low detection limit (72 nM), fast response time (30 s), wide pH operating range (6-8), great tissue penetration, large Stokes shift (125 nm) and 291-fold fluorescence enhancement at 475 nm in the mapping of ClO. Probe could trace amounts of exogenous and endogenous ClO with high sensitivity in MCF-7 cells and HeLa cells. Expectantly, the fluoxetine-induced liver injury model is successfully established, and probe has been used for detecting the fluctuation of ClO levels in the mouse model of fluoxetine-induced liver injury. All in all, probe with its high specificity, good biological compatibility and liver tissue penetration ability is expected to assist with the early diagnosis of DILI and the clinical screening of various new drugs. We expect that probe could be efficiently used as a powerful molecular tool to predict clinical DILI and explore molecular mechanisms between molecules and disease.

摘要

在过去的几十年中,由于药物滥用,药物性肝损伤 (DILI) 已成为一个严重的公共卫生问题。在各种活性氧物种中,越来越多的证据表明 ClO 已被用作 DILI 的潜在生物标志物。在这项工作中,通过用 -二甲基硫代氨基甲酸盐修饰 4'-羟基联苯-4-甲腈 (染料 ),设计并合成了一种新的“开启”荧光探针 ,以作为检测 ClO 的响应位点。探针 在检测 ClO 时具有低检测限 (72 nM)、快速响应时间 (30 s)、宽 pH 工作范围 (6-8)、出色的组织穿透能力、大斯托克斯位移 (125nm) 和在 MCF-7 细胞和 HeLa 细胞中在 475nm 处荧光增强 291 倍。探针 可以高灵敏度地追踪 MCF-7 细胞和 HeLa 细胞中外源和内源性 ClO。预计,成功建立了氟西汀诱导的肝损伤模型,并使用探针 检测了氟西汀诱导的肝损伤小鼠模型中 ClO 水平的波动。总之,探针 具有高特异性、良好的生物相容性和肝组织穿透能力,有望协助 DILI 的早期诊断和各种新药的临床筛选。我们期望探针 能够有效地用作预测临床 DILI 和探索分子与疾病之间分子机制的有力分子工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86c1/10377358/992c6473758a/biosensors-13-00744-g001.jpg

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