Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier

Due to the physical and physiological properties of the blood-brain barrier (BBB), the transport of neurotherapeutics from blood to brain is still a pharmaceutical challenge. We previously conducted a series of experiments to explore the potential of the anti-transferrin receptor 8D3 monoclonal anti...

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Autores: Cabezón Rodríguez, Itsaso, Augé Marí, Elisabet, Bosch Marimon, Manel, Beckett, Alison J., Prior, Ian A., Pelegrí i Gabaldà, Carme, Vilaplana i Hortensi, Jordi
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2017
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/168958
Acesso em linha:https://hdl.handle.net/2445/168958
Access Level:acceso abierto
Palavra-chave:Barrera hematoencefàlica
Nanopartícules
Blood-brain barrier
Nanoparticles
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spelling Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrierCabezón Rodríguez, ItsasoAugé Marí, ElisabetBosch Marimon, ManelBeckett, Alison J.Prior, Ian A.Pelegrí i Gabaldà, CarmeVilaplana i Hortensi, JordiBarrera hematoencefàlicaNanopartículesBlood-brain barrierNanoparticlesDue to the physical and physiological properties of the blood-brain barrier (BBB), the transport of neurotherapeutics from blood to brain is still a pharmaceutical challenge. We previously conducted a series of experiments to explore the potential of the anti-transferrin receptor 8D3 monoclonal antibody (mAb) to transport neurotherapeutics across the BBB. In that study, gold nanoparticles (AuNPs) were coated with the 8D3 antibody and administered intravenously to mice. Transmission electron microscopy was used and a two-dimensional (2D) image analysis was performed to detect the AuNPs in the brain capillary endothelial cells (BCECs) and brain parenchyma. In the present work, we determined that serial block-face scanning electron microscopy (SBF-SEM) is a useful tool to study the transcytosis of these AuNPs across the BBB in three dimensions and we, therefore, applied it to gain more knowledge of their transcellular trafficking. The resulting 3D reconstructions provided additional information on the endocytic vesicles containing AuNPs and the endosomal processing that occurs inside BCECs. The passage from 2D to 3D analysis reinforced the trafficking model proposed in the 2D study, and revealed that the vesicles containing AuNPs are significantly larger and more complex than described in our 2D study. We also discuss tradeoffs of using this technique for our application, and conclude that together with other volume electron microscopy imaging techniques, SBF-SEM is a powerful approach that is worth of considering for studies of drug transport across the BBB.Springer Verlag2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/168958Articles publicats en revistes (Bioquímica i Fisiologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1007/s00418-017-1553-9Histochemistry and Cell Biology, 2017, vol. 148, p. 3-12https://doi.org/10.1007/s00418-017-1553-9(c) Springer Verlag, 2017info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1689582026-05-27T06:46:51Z
dc.title.none.fl_str_mv Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
title Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
spellingShingle Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
Cabezón Rodríguez, Itsaso
Barrera hematoencefàlica
Nanopartícules
Blood-brain barrier
Nanoparticles
title_short Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
title_full Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
title_fullStr Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
title_full_unstemmed Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
title_sort Serial block-face scanning electron microscopy applied to study the trafficking of 8D3-coated gold nanoparticles at the blood-brain barrier
dc.creator.none.fl_str_mv Cabezón Rodríguez, Itsaso
Augé Marí, Elisabet
Bosch Marimon, Manel
Beckett, Alison J.
Prior, Ian A.
Pelegrí i Gabaldà, Carme
Vilaplana i Hortensi, Jordi
author Cabezón Rodríguez, Itsaso
author_facet Cabezón Rodríguez, Itsaso
Augé Marí, Elisabet
Bosch Marimon, Manel
Beckett, Alison J.
Prior, Ian A.
Pelegrí i Gabaldà, Carme
Vilaplana i Hortensi, Jordi
author_role author
author2 Augé Marí, Elisabet
Bosch Marimon, Manel
Beckett, Alison J.
Prior, Ian A.
Pelegrí i Gabaldà, Carme
Vilaplana i Hortensi, Jordi
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Barrera hematoencefàlica
Nanopartícules
Blood-brain barrier
Nanoparticles
topic Barrera hematoencefàlica
Nanopartícules
Blood-brain barrier
Nanoparticles
description Due to the physical and physiological properties of the blood-brain barrier (BBB), the transport of neurotherapeutics from blood to brain is still a pharmaceutical challenge. We previously conducted a series of experiments to explore the potential of the anti-transferrin receptor 8D3 monoclonal antibody (mAb) to transport neurotherapeutics across the BBB. In that study, gold nanoparticles (AuNPs) were coated with the 8D3 antibody and administered intravenously to mice. Transmission electron microscopy was used and a two-dimensional (2D) image analysis was performed to detect the AuNPs in the brain capillary endothelial cells (BCECs) and brain parenchyma. In the present work, we determined that serial block-face scanning electron microscopy (SBF-SEM) is a useful tool to study the transcytosis of these AuNPs across the BBB in three dimensions and we, therefore, applied it to gain more knowledge of their transcellular trafficking. The resulting 3D reconstructions provided additional information on the endocytic vesicles containing AuNPs and the endosomal processing that occurs inside BCECs. The passage from 2D to 3D analysis reinforced the trafficking model proposed in the 2D study, and revealed that the vesicles containing AuNPs are significantly larger and more complex than described in our 2D study. We also discuss tradeoffs of using this technique for our application, and conclude that together with other volume electron microscopy imaging techniques, SBF-SEM is a powerful approach that is worth of considering for studies of drug transport across the BBB.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/168958
url https://hdl.handle.net/2445/168958
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/s00418-017-1553-9
Histochemistry and Cell Biology, 2017, vol. 148, p. 3-12
https://doi.org/10.1007/s00418-017-1553-9
dc.rights.none.fl_str_mv (c) Springer Verlag, 2017
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Springer Verlag, 2017
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Fisiologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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