Spatially resolved determination of the abundance of the HER2 marker in microscopic breast tumors using targeted SERS imaging

• Published in: Mikrochimica acta (1966) Vol. 188; no. 9; p. 288
• Main Authors: Verdin, Alexandre, Malherbe, Cedric, Eppe, Gauthier
• Format: Journal Article Web Resource
• Language: English
• Published: Vienna Springer Vienna 01.09.2021; Springer; Springer Nature B.V
• Subjects: Analytical Chemistry; Antigens; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; breast tumor detection; Cell membranes; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Chimie; Digital imaging; Female; Gold; Growth factors; HER2; Heterogeneity; Humans; IHC; Image analysis; Markers; Metal Nanoparticles - chemistry; Microengineering; Monoclonal antibodies; Multiplexing; Nanochemistry; Nanomaterials for biomedical imaging and targeting; Nanoparticles; Nanotechnology; Original Paper; Physical, chemical, mathematical & earth Sciences; Physique, chimie, mathématiques & sciences de la terre; quantitative molecular imaging; Raman Spectroscopy; Receptor, ErbB-2 - metabolism; SERS; Silver; Spectrum Analysis, Raman - methods; Tumors; Nanoparticles; Quantitative molecular imaging; SERS; Breast tumor detection; IHC; Raman spectrometry; HER2; Cancer
• ISSN: 0026-3672; 1436-5073; 1436-5073
• DOI: 10.1007/s00604-021-04943-6

Highly selective nanoprobes have been developed based on SERS-active Au@Ag nanoparticles protected by a PEG coating and functionalized with monoclonal antibodies against human epidermal growth factor receptor 2 (HER2). The PEG coating allows to drastically reduce unspecific interactions during incubation on tissues, while the monoclonal antibodies allow a highly specific targeting of HER2. Using the designed SERS nanoprobes combined with a spectral imaging and data weighting approach, we demonstrate the proportionality between the SERS signal and the amount of HER2 antigen on the cell membranes as measured by digital image analysis of IHC staining in microscopic breast tumors (linear fit R 2 = 0.87). We also show that the level of expression of HER2 measured by SERS is significantly different between several microscopic tumor parts of the same tissue slide. Therefore, SERS is proving to be a suitable technique for the localized quantitative measurement of specific markers in breast cancerous tissues. Owing to its high multiplexing capabilities, SERS could be a future tool of choice for characterizing the molecular heterogeneity of tumors at the microscopic scale. Graphical abstract