Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots

Abstract Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent...

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Autores principales:	Fernanda Ramos-Gomes, Julia Bode, Alyona Sukhanova, Svetlana V. Bozrova, Mara Saccomano, Miso Mitkovski, Julia Eva Krueger, Anja K. Wege, Walter Stuehmer, Pavel S. Samokhvalov, Daniel Baty, Patrick Chames, Igor Nabiev, Frauke Alves
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31f241baea3d44148c2b495267e0f415
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spelling	oai:doaj.org-article:31f241baea3d44148c2b495267e0f4152021-12-02T15:05:17ZSingle- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots10.1038/s41598-018-22973-82045-2322https://doaj.org/article/31f241baea3d44148c2b495267e0f4152018-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-22973-8https://doaj.org/toc/2045-2322Abstract Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent quantum dots (QDs) for single- and two-photon detection and imaging of human micrometastases and disseminated tumour cells in ex vivo biological samples of breast and pancreatic metastatic tumour mouse models expressing human epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen (CEA). By staining thin (5–10 µm) paraffin and thick (50 µm) agarose tissue sections, we detected HER2- and CEA-positive human tumour cells infiltrating the surrounding tissues or metastasizing to different organs, including the brain, testis, lung, liver, and lymph nodes. Compared to conventional fluorescently labelled antibodies the sdAb-HER2-QD and sdAb-CEA-QD nanoprobes are superior in detecting micrometastases in tissue sections by lower photobleaching and higher brightness of fluorescence signals ensuring much better discrimination of positive signals versus background. Very high two-photon absorption cross-sections of QDs and small size of the nanoprobes ensure efficient imaging of thick tissue sections unattainable with conventional fluorescent probes. The nanobody–QD probes will help to improve early cancer diagnosis and prognosis of progression by assessing metastasis.Fernanda Ramos-GomesJulia BodeAlyona SukhanovaSvetlana V. BozrovaMara SaccomanoMiso MitkovskiJulia Eva KruegerAnja K. WegeWalter StuehmerPavel S. SamokhvalovDaniel BatyPatrick ChamesIgor NabievFrauke AlvesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fernanda Ramos-Gomes Julia Bode Alyona Sukhanova Svetlana V. Bozrova Mara Saccomano Miso Mitkovski Julia Eva Krueger Anja K. Wege Walter Stuehmer Pavel S. Samokhvalov Daniel Baty Patrick Chames Igor Nabiev Frauke Alves Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
description	Abstract Early detection of malignant tumours and, especially, micrometastases and disseminated tumour cells is still a challenge. In order to implement highly sensitive diagnostic tools we demonstrate the use of nanoprobes engineered from nanobodies (single-domain antibodies, sdAbs) and fluorescent quantum dots (QDs) for single- and two-photon detection and imaging of human micrometastases and disseminated tumour cells in ex vivo biological samples of breast and pancreatic metastatic tumour mouse models expressing human epidermal growth factor receptor 2 (HER2) or carcinoembryonic antigen (CEA). By staining thin (5–10 µm) paraffin and thick (50 µm) agarose tissue sections, we detected HER2- and CEA-positive human tumour cells infiltrating the surrounding tissues or metastasizing to different organs, including the brain, testis, lung, liver, and lymph nodes. Compared to conventional fluorescently labelled antibodies the sdAb-HER2-QD and sdAb-CEA-QD nanoprobes are superior in detecting micrometastases in tissue sections by lower photobleaching and higher brightness of fluorescence signals ensuring much better discrimination of positive signals versus background. Very high two-photon absorption cross-sections of QDs and small size of the nanoprobes ensure efficient imaging of thick tissue sections unattainable with conventional fluorescent probes. The nanobody–QD probes will help to improve early cancer diagnosis and prognosis of progression by assessing metastasis.
format	article
author	Fernanda Ramos-Gomes Julia Bode Alyona Sukhanova Svetlana V. Bozrova Mara Saccomano Miso Mitkovski Julia Eva Krueger Anja K. Wege Walter Stuehmer Pavel S. Samokhvalov Daniel Baty Patrick Chames Igor Nabiev Frauke Alves
author_facet	Fernanda Ramos-Gomes Julia Bode Alyona Sukhanova Svetlana V. Bozrova Mara Saccomano Miso Mitkovski Julia Eva Krueger Anja K. Wege Walter Stuehmer Pavel S. Samokhvalov Daniel Baty Patrick Chames Igor Nabiev Frauke Alves
author_sort	Fernanda Ramos-Gomes
title	Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
title_short	Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
title_full	Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
title_fullStr	Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
title_full_unstemmed	Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
title_sort	single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/31f241baea3d44148c2b495267e0f415
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Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dots

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