ROS/pH双重响应的β-咔啉类探针H8DP的构建及肿瘤荧光成像研究  

The construction of ROS/pH dual-responsiveβ-carboline probe H8DP and research on tumor selective fluorescence imaging

作　　者：单文配 陈实 刘云 王晨 李洋阳 张延安 凌勇[1,2] SHAN Wenpei;CHEN Shi;LIU Yun;WANG Chen;LI Yangyang;ZHANG Yanan;LING Yong(Medical School,Nantong University,Jiangsu 226001;School of Pharmacy,Nantong University,Jiangsu 226001)

机构地区：[1]南通大学医学院,江苏226001 [2]南通大学药学院,江苏226001

出　　处：《交通医学》2021年第4期329-333,共5页Medical Journal of Communications

基　　金：国家自然科学基金面上项目(21977058)。

摘　　要：目的:设计、合成活性氧(ROS)/pH双重响应的β-咔啉类小分子荧光探针H8DP,为肿瘤早期诊断提供新的思路。方法:初始原料L-色氨酸和3,4,5-三甲氧基苯甲醛经过环合、氧化、酰肼化、叠氮重排等多步反应得到H8N,再与对硝基苯基氯甲酸酯反应生成活性酯,最后与4-羟甲基苯硼酸频哪醇酯反应得到目标化合物H8DP。采用紫外和荧光光谱研究H8DP的ROS/pH响应性,并从细胞和动物水平评价其肿瘤选择性荧光成像。结果:H8DP在低pH和高ROS水平下产生显著荧光,并能在Hela细胞和小鼠肿瘤组织中选择性成像,实现对肿瘤组织“开-关”模式荧光成像。结论:构建的H8DP具有ROS/pH双重响应性,能在肿瘤组织中选择性荧光成像,为肿瘤早期诊断提供新的思路。Objective:To provide a new idea for the early diagnosis of tumor,we designed and synthesized a ROS/pH dual-responsive small molecule fluorescent probe H8DP based onβ-carboline.Methods:The starting materials L-tryptophan and 3,4,5-trimethoxybenzaldehyde generated H8N through cyclization,oxidation,hydrazidation and azide rearrangement reactions.Then H8N reacted with p-nitrophenyl chloroformate to generate active ester,and finally reacted with 4-(hydroxymethyl)phenylboronic acid pinacol ester to obtain the target compound H8DP.We used UV and fluorescence spectroscopy to study the pH/ROS responsiveness of H8DP,and evaluated its selective fluorescence imaging at the cellular and animal levels.Results:H8DP produced significant fluorescence at low pH and high ROS levels,and performed selective imaging in Hela cells and mouse tumor tissues to achieve“on-off”fluorescence imaging of tumor tissues.Conclusion:The compound H8DP in this article possesses dual ROS/pH responsiveness and can perform selective fluorescence imaging in tumor tissues,providing new ideas for early tumor diagnosis.

关 键 词：肿瘤诊断 β-咔啉 PH敏感 活性氧响应 荧光成像 

分 类 号：R730.4[医药卫生—肿瘤]