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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2018-03-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-018-22973-8 |
id |
doaj-31f241baea3d44148c2b495267e0f415 |
---|---|
record_format |
Article |
spelling |
doaj-31f241baea3d44148c2b495267e0f4152020-12-08T03:23:15ZengNature Publishing GroupScientific Reports2045-23222018-03-018111210.1038/s41598-018-22973-8Single- and two-photon imaging of human micrometastases and disseminated tumour cells with conjugates of nanobodies and quantum dotsFernanda Ramos-Gomes0Julia Bode1Alyona Sukhanova2Svetlana V. Bozrova3Mara Saccomano4Miso Mitkovski5Julia Eva Krueger6Anja K. Wege7Walter Stuehmer8Pavel S. Samokhvalov9Daniel Baty10Patrick Chames11Igor Nabiev12Frauke Alves13Translational Molecular Imaging Group, Max Planck Institute for Experimental MedicineTranslational Molecular Imaging Group, Max Planck Institute for Experimental MedicineLaboratoire de Recherche en Nanosciences (LRN-EA4682), Université de Reims Champagne-ArdenneLaboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)Translational Molecular Imaging Group, Max Planck Institute for Experimental MedicineLight Microscopy Facility, Max Planck Institute for Experimental MedicineTranslational Molecular Imaging Group, Max Planck Institute for Experimental MedicineDepartment of Gynecology and Obstetrics, University Medical Center RegensburgEmeritus Optogenetic Group, Max Planck Institute for Experimental MedicineLaboratory of Nano-Bioengineering, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute)Aix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCMAix Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCMLaboratoire de Recherche en Nanosciences (LRN-EA4682), Université de Reims Champagne-ArdenneTranslational Molecular Imaging Group, Max Planck Institute for Experimental MedicineAbstract 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.https://doi.org/10.1038/s41598-018-22973-8 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-03-01 |
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. |
url |
https://doi.org/10.1038/s41598-018-22973-8 |
work_keys_str_mv |
AT fernandaramosgomes singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT juliabode singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT alyonasukhanova singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT svetlanavbozrova singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT marasaccomano singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT misomitkovski singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT juliaevakrueger singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT anjakwege singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT walterstuehmer singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT pavelssamokhvalov singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT danielbaty singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT patrickchames singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT igornabiev singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots AT fraukealves singleandtwophotonimagingofhumanmicrometastasesanddisseminatedtumourcellswithconjugatesofnanobodiesandquantumdots |
_version_ |
1724392480356433920 |