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

• Published in: Mikrochimica acta (1966) Vol. 186; no. 7; p. 439
• Main Authors: Yang, Tiantian, Xu, Lulu, Liu, Shengchun, Shen, Yifan, Huang, Lizhen, Zhang, Lutan, Ding, Shijia, Cheng, Wei
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.07.2019; Springer
• Subjects: Analytical Chemistry; Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - genetics; Aptamers, Nucleotide - metabolism; Atomic force microscopy; Cancer; Care and treatment; Cell Line, Tumor; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Dendrimers - chemistry; DNA; DNA - chemistry; DNA - genetics; Fluoresceins - chemistry; Fluorescence microscopy; Fluorescent Dyes - chemistry; Formaldehyde; Health aspects; Humans; Microengineering; Microscopy, Fluorescence - methods; Nanochemistry; Nanostructures - chemistry; Nanotechnology; Nucleic Acid Hybridization; Original Paper; Pertuzumab; Proof of Concept Study; Protein Multimerization; Receptor, ErbB-2 - chemistry; Receptor, ErbB-2 - metabolism; DNA nanoassembly; Cancer diagnostics; Proximity hybridization; Formalin-fixed paraffin-embedded tissue; Hairpin-free nonlinear HCR; Aptamer; Breast cancer; HER2 dimerization; Fluorescent imaging
• ISSN: 0026-3672; 1436-5073
• DOI: 10.1007/s00604-019-3549-8

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. Graphical abstract Schematic presentation of amplified imaging of human epidermal growth factor receptor 2 (HER2) dimerization on cancer cell surfaces by using a co-localization triggered DNA nanoassembly (CtDNA).