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针对受体酪氨酸激酶的离子荧光传感器,用于生物系统成像和流式细胞术应用。

Ionic fluorescent sensor targeting receptor tyrosine kinases for biosystems imaging and application in flow cytometry.

机构信息

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, China; College of Medical Laboratory, Dalian Medical University, Dalian, 116044, China.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, 116024, China.

出版信息

Biosens Bioelectron. 2020 Apr 1;153:112026. doi: 10.1016/j.bios.2020.112026. Epub 2020 Jan 15.

Abstract

Fluorescent imaging of receptor tyrosine kinases in living biosystems is an important means for the early diagnosis of cancer, herein an ionic fluorescent sensor (SNB) composed of targeting unit (sunitinib) and nile blue fluorophore linked via long flexible chain has been designed and evaluated. The SNB sensor exhibits distinct fluorescence responses to receptor tyrosine kinases derived from unfolding strategy and targeting ability, which were evaluated through 2D NMR analyses, optical studies, kinase activity assays. The SNB sensor has excellent membrane fluorescent imaging by electrostatic adsorption and can selectively insert into receptor tyrosine kinases domain pocket on the membrane of cancer cell lines. The SNB sensor has been successfully applied in flow cytometry for cell sorting and fluorescence imaging with tumor mouse model in vivo. The SNB senor may help transition the technology into a widely suitable tool for flow cytometry, imaging with confocal microscopes, whole animal imaging and possibly facilitating early diagnoses and treatment of cancer.

摘要

在活体生物系统中对受体酪氨酸激酶进行荧光成像,是癌症早期诊断的重要手段。本文设计并评价了一种由靶向单元(舒尼替尼)和通过长柔性链连接的尼罗蓝荧光团组成的离子荧光传感器(SNB)。SNB 传感器通过展开策略和靶向能力表现出对受体酪氨酸激酶的明显荧光响应,通过二维 NMR 分析、光学研究、激酶活性测定进行了评价。SNB 传感器通过静电吸附具有出色的膜荧光成像能力,并可以选择性地插入癌细胞系膜上受体酪氨酸激酶结构域的口袋中。SNB 传感器已成功应用于流式细胞术分选细胞,以及在肿瘤小鼠模型的体内荧光成像。SNB 传感器可能有助于将该技术转化为流式细胞术、共聚焦显微镜成像、全动物成像的广泛适用工具,并可能有助于癌症的早期诊断和治疗。

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