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

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Abstract

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.

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).

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Acknowledgments

This work was funded by the National Natural Science Foundation of China (81572080, 81873972 and 81873980) and the Training Program for Advanced Young Medical Personnel of Chongqing (2017HBRC003).

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Authors and Affiliations

  1. The Center for Clinical Molecular Medical detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Tiantian Yang, Lulu Xu, Yifan Shen, Lizhen Huang, Lutan Zhang & Wei Cheng

  2. Department of Endocrine and Breast Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Shengchun Liu

  3. Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Shijia Ding

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  1. Tiantian Yang
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Correspondence to Shijia Ding or Wei Cheng.

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Yang, T., Xu, L., Liu, S. et al. Amplified fluorescence imaging of HER2 dimerization on cancer cells by using a co-localization triggered DNA nanoassembly. Microchim Acta 186, 439 (2019). https://doi.org/10.1007/s00604-019-3549-8

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