A NIR turn-on fluorescent probe applied in cytochrome P450 reductase detection and hypoxia imaging in tumor cells
A NIR turn-on fluorescent probe applied in cytochrome P450 reductase detection and hypoxia imaging in tumor cells
复制标题
近红外开启荧光探针应用于肿瘤细胞细胞色素P450还原酶检测和缺氧成像
DOI：
10.1016/j.dyepig.2016.12.062
复制
发表时间：
2017-04-01
影响因子：
4.5
通讯作者：
Huang, Junhai
中科院分区：
文献类型：
--
作者：
Cui, Lei;Shi, Yanping;Huang, Junhai
迫切需要对缺氧区域进行体内监测。具有优异光稳定性的近红外（NIR）荧光活性荧光团优选用于体内成像。设计合成了一种新型的高选择性、长波长的荧光探针，并将其应用于生物还原酶（肿瘤细胞中过表达的细胞色素P450还原酶）和缺氧检测。NIR探针（AZO-DCM）基于光稳定性荧光团二氰基亚甲基-4H-吡喃染料（DCM），偶氮键作为探针猝灭剂和缺氧触发剂。该探针与细胞色素P450还原酶反应后，偶氮键断裂，DCM释放，荧光发光，具有良好的抗干扰能力，不受生物硫醇、无机盐（包括亚硫酸盐）和氨基酸等多种干扰物质的干扰。AZO-DCM对细胞色素P450还原酶和缺氧具有良好的选择性和敏感性。在细胞色素P450还原酶和NADH体系的作用下，荧光强度在4 min内增强了150倍以上，HPLC实验也证实了反应机理。AZO-DCM探针在体内肿瘤细胞缺氧状态的检测中表现出良好的特性。(C)2016爱思唯尔有限公司版权所有
In vivo monitoring of the hypoxic area is urgently required. Near infrared (NIR) fluorescence-active fluorophores with excellent photo stability are preferable for in vivo imaging. A novel rational designed turn-on fluorescent probe with high selectivity and long-wavelength was synthesized which was applied in bioreductase (cytochrome P450 reductase which overexpressed in tumor cells) and hypoxia detection. The NIR probe (AZO-DCM) is based on a photo stability fluorophore dicyanomethylene-4H-pyran dye (DCM) with an azo bond as probe quencher and hypoxic trigger. After reacted with cytochrome P450 reductase, azo bond was cleaved and DCM released with fluorescent on. The designed probe showed high anti-interference ability which cannot disturb by many interfering substances, such as biothiols, inorganic salts (included sulfite salt) and amino acid. AZO-DCM performed good selectivity and sensitivity to cytochrome P450 reductase and hypoxia. The fluorescent intensity was increased more than 150-fold after response to cytochrome P450 reductase and NADH system in 4 min. The reaction mechanism also proved by HPLC experiment. Probe AZO-DCM displayed excellent properties in identifying different hypoxic status of tumor cells in vivo. (C) 2016 Elsevier Ltd. All rights reserved.