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利用一种 pH 激活的溶酶体靶向荧光探针对癌细胞进行选择性成像。

Selective imaging of cancer cells with a pH-activatable lysosome-targeting fluorescent probe.

机构信息

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, 210093, People's Republic of China.

出版信息

Anal Chim Acta. 2017 Oct 2;988:66-73. doi: 10.1016/j.aca.2017.07.055. Epub 2017 Jul 31.

Abstract

Fluorescence imaging with tumor-specific fluorescent probe has emerged as a tool to aid surgeons in the identification and removal of tumor tissue. We report here a new lysosome-targeting fluorescent probe (NBOH) with BODIPY fluorephore to distinguish tumor tissue out of normal tissue based on different pH environment. The probe exhibited remarkable pH-dependent fluorescence behavior in a wide pH range from 3.0 to 11.0, especially a sensitive pH-dependent fluorescence change at pH range between 3.5 and 5.5, corresponding well to the acidic microenvironment of tumor cells, in aqueous solution. The response time of NBOH was extremely short and the photostability was proved to be good. Toxicity test and fluorescence cell imaging together with a sub-cellular localization study were carried out revealing its low biotoxicity and good cell membrane permeability. And NBOH was successfully applied to the imaging of tumor tissue in tumor-bearing mice suggesting potential application to surgery as a tumor-specific probe.

摘要

荧光成像是一种利用肿瘤特异性荧光探针来辅助外科医生识别和切除肿瘤组织的工具。我们在这里报告了一种新的溶酶体靶向荧光探针(NBOH),它带有 BODIPY 荧光团,可以根据不同的 pH 环境,将肿瘤组织与正常组织区分开来。该探针在从 3.0 到 11.0 的很宽的 pH 范围内表现出显著的 pH 依赖性荧光行为,特别是在 pH 3.5 到 5.5 之间的 pH 依赖性荧光变化非常敏感,这与肿瘤细胞的酸性微环境相吻合,在水溶液中。NBOH 的响应时间极短,光稳定性良好。毒性试验和荧光细胞成像以及亚细胞定位研究表明,它具有低细胞毒性和良好的细胞膜通透性。并且,NBOH 成功地应用于荷瘤小鼠的肿瘤组织成像,这表明它有可能作为一种肿瘤特异性探针应用于手术。

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