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

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Abstract

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 R2 = 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.

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Acknowledgements

The authors acknowledge the University Hospital Biobank of the University of Liège for providing the samples, performing the IHC staining, and obtaining high resolution images of the IHC slides.

Funding

Cedric Malherbe acknowledges the F.R.S-FNRS for funding (Research Associate fellowship).

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  1. Mass Spectrometry Laboratory, MolSys Research Unit, University of Liège, 4000, Liège, Belgium

    Alexandre Verdin, Cedric Malherbe & Gauthier Eppe

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  1. Alexandre Verdin
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  2. Cedric Malherbe
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  3. Gauthier Eppe
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Correspondence to Gauthier Eppe.

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All samples were provided with the approval of the University Hospital Ethics Committee (Ref 2017/236).

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Verdin, A., Malherbe, C. & Eppe, G. Spatially resolved determination of the abundance of the HER2 marker in microscopic breast tumors using targeted SERS imaging. Microchim Acta 188, 288 (2021). https://doi.org/10.1007/s00604-021-04943-6

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