智能型金纳米棒荧光探针的制备及其肿瘤细胞成像研究  

Preparation of A Novel Smart Gold Nanorod Probe and Its Application in Cancer Cell Imaging

作　　者：尹玲 王安娜[3] 赵梦 沙靖全 白永香[4] 史海斌 Yin Ling;Wang Anna;Zhao Meng;Sha Jingquan;Bai Yongxiang;Shi Haibin(State Key Laboratory of Radiation Medicine and Protection,School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsa Higher Education Institutions, Soochow University,Suzhou 215123;Key Laboratory of Organic Synthesis of Jiangsu Province,College of Chemistry,Chemical Engineering and Materials Science,Soochow University,Suzhou 215123;Department of Chemistry and Chemical Engineering,Jining University,Qufu 273155;School of Biology and Basic Medical Sciences,Soochow University,Suzhou 215123)

机构地区：[1]苏州大学江苏省有机合成重点实验室苏州大学材料与化学化工学部,苏州215123 [2]济宁学院化学与化工系,曲阜273155 [3]苏州大学放射医学与辐射防护国家重点实验室苏州大学医学部放射医学与防护学院江苏省高校放射医学协同创新中心,苏州215123 [4]苏州大学医学部基础医学与生物科学学院,苏州215123

出　　处：《化学通报》2019年第1期44-50,1,共8页Chemistry

基　　金：国家重点研发计划项目(2016YFC0101200);国家自然科学基金项目(21572153);江苏省重点研发计划(社会发展)项目(BE2018655);山东省高等学校优势学科人才团队培育计划资助

摘　　要：开发能特异和灵敏检测基质金属蛋白酶-2(MMP-2)的智能型荧光分子探针,对于癌症的早期精准诊断与治疗至关重要。本文基于MMP-2特异性识别的多肽底物,利用一价铜离子催化的"点击"化学反应将荧光素(FITC)和多肽底物GPLGVRGY相偶联,与SH-PEG-COOH修饰的金纳米棒在EDC和Sulfo-NHS的作用下通过酰胺化反应,制备得到一种新的MMP-2特异性响应的荧光共振能量转移(FRET)金纳米棒探针GNR@FITC。体外重组酶检测实验、MTT实验及细胞共聚焦显微成像结果表明,该探针对MMP-2过表达小鼠乳腺癌细胞4T1表现出较好的特异性和检测灵敏度,具有进一步开发应用于乳腺癌早期诊断的极大潜力。Developing a smart fluorescent probe which can specifically and sensitively detect matrix metalloproteinases-2( MMP-2) is vital for the early accurate diagnosis and treatment of cancers. In this study,fluorescein isothiocyanate( FITC) was firstly conjugated to the peptide substrate GPLGVRGY by using copper( I)-catalyzed"click"reaction,and subsequently reacted with gold nanorods decorated with SH-PEG-COOH under the catalysis of EDC and Sulfo-NHS through amidation reaction to afford a novel fluorescence resonance energy transfer( FRET)-based probe GNR@ FITC for specific detection of MMP-2. In vitro enzyme detection experiments,MTT assays and fluorescence imaging results showed that the probe shows good specificity and high sensitivity for the detection of MMP-2-overexpressed 4 T1 cells,which may have great potential for clinical application in early diagnosis of breast cancer.

关 键 词：基质金属蛋白酶-2 金纳米棒 荧光共振能量转移 分子探针 荧光成像 

分 类 号：R73-3[医药卫生—肿瘤] O657.3[医药卫生—临床医学]