Microchimica Acta

, 186:439 | Cite as

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

  • Tiantian Yang
  • Lulu Xu
  • Shengchun Liu
  • Yifan Shen
  • Lizhen Huang
  • Lutan Zhang
  • Shijia DingEmail author
  • Wei ChengEmail author
Original Paper


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).


HER2 dimerization Fluorescent imaging Aptamer Proximity hybridization Hairpin-free nonlinear HCR DNA nanoassembly Formalin-fixed paraffin-embedded tissue Breast cancer Cancer diagnostics 



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).

Compliance with ethical standards

The author(s) declare that they have no competing interests.

Supplementary material

604_2019_3549_MOESM1_ESM.docx (1.3 mb)
ESM 1 (DOCX 1.30 mb)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Center for Clinical Molecular Medical detectionThe First Affiliated Hospital of Chongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.Department of Endocrine and Breast Surgery, The First Affiliated HospitalChongqing Medical UniversityChongqingPeople’s Republic of China
  3. 3.Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory MedicineChongqing Medical UniversityChongqingPeople’s Republic of China

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