Amplified fluorescence imaging of HER2 dimerization on cancer cells by using a co-localization triggered DNA nanoassembly

被引:12
作者
Yang, Tiantian [1 ]
Xu, Lulu [1 ]
Liu, Shengchun [2 ]
Shen, Yifan [1 ]
Huang, Lizhen [1 ]
Zhang, Lutan [1 ]
Ding, Shijia [3 ]
Cheng, Wei [1 ]
机构
[1] Chongqing Med Univ, Affiliated Hosp 1, Ctr Clin Mol Med Detect, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrine & Breast Surg, Chongqing 400016, Peoples R China
[3] Chongqing Med Univ, Coll Lab Med, Minist Educ, Key Lab Clin Lab Diagnost, Chongqing 400016, Peoples R China
基金
中国国家自然科学基金;
关键词
HER2; dimerization; Fluorescent imaging; Aptamer; Proximity hybridization; Hairpin-free nonlinear HCR; DNA nanoassembly; Formalin-fixed paraffin-embedded tissue; Breast cancer; Cancer diagnostics; BREAST-CANCER; PROXIMITY ASSAY; EXPRESSION; APTAMER; GROWTH;
D O I
10.1007/s00604-019-3549-8
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Convenient and sensitive detection of human epidermal growth factor receptor 2 (HER2) dimerization is highly desirable for molecule subtyping and guiding personalized HER2 targeted therapy of breast cancer. A colocalization-triggered DNA nanoassembly (CtDNA) strategy was developed for amplified imaging of HER2 dimerization. It exploits (a) the advantage of the specificity of aptamer proximity hybridization, and (b) the high sensitivity of hairpin-free nonlinear HCR. The mechanism of step-by-step hairpin-free nonlinear HCR for DNA dendritic nanoassembly was studied by native polyacrylamide gel electrophoresis, atomic force microscopy and fluorometry. The results revealed a high specificity, sensitivity, and excellent controllability of the DNA dendritic nanoassembly. The method was used to identify HER2 homodimers and HER2/HER3 heterodimers in various breast cancer cell lines using fluorescence microscopy. It was then extended to image and quantitatively evaluate HER2 homodimers in clinical formalin-fixed paraffin-embedded breast cancer tissue specimens. This revealed its remarkable accuracy and practicality for clinical diagnostics.
引用
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页数:10
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