In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia

The use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in...

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Autores: Agulla, Jesús, Brea, David, Campos, Francisco|||0000-0001-8665-1039, Sobrino, Tomás|||0000-0002-9760-8690, Argibay, Bárbara, Al-Soufi, Wajih, Blanco, Miguel, Castillo, José, Ramos-Cabrer, Pedro|||0000-0003-0368-7031
Tipo de documento: artigo
Data de publicação:2013
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:184986
Acesso em linha:https://ddd.uab.cat/record/184986
https://dx.doi.org/urn:doi:10.7150/thno.7088
Access Level:Acceso aberto
Palavra-chave:Cerebral ischemia
Peri-infarct region
MRI
Theranostics
Drug delivery
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spelling In Vivo Theranostics at the Peri-Infarct Region in Cerebral IschemiaAgulla, JesúsBrea, DavidCampos, Francisco|||0000-0001-8665-1039Sobrino, Tomás|||0000-0002-9760-8690Argibay, BárbaraAl-Soufi, WajihBlanco, MiguelCastillo, JoséRamos-Cabrer, Pedro|||0000-0003-0368-7031Cerebral ischemiaPeri-infarct regionMRITheranosticsDrug deliveryThe use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries. We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment. We confirmed that the HSP72 protein is a suitable biomarker for the peri-infarct region, as it is selectively expressed by at-risk tissue for up to 7 days following cerebral ischemia. We also describe the development of anti-HSP72 vectorized stealth immunoliposomes containing imaging probes to make them traceable by conventional imaging techniques (fluorescence and MRI) that were used to encapsulate a therapeutic agent (citicoline) for the treatment of cerebral ischemia. We tested the molecular recognition capabilities of these nano-platforms in vitro together with their diagnostic and therapeutic properties in vivo, in an animal model of cerebral ischemia. Using MRI, we found that 80% of vectorized liposomes were located on the periphery of the ischemic lesion, and animals treated with citicoline encapsulated on these liposomes presented lesion volumes up to 30% smaller than animals treated with free (non-encapsulated) drugs. Our results show the potential of nanotechnology for the development of effective tools for the treatment of neurological diseases. 22013-01-0120132013-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/184986https://dx.doi.org/urn:doi:10.7150/thno.7088reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI11-02161Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP09-00074Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2008-02190Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2011-30517Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RETICS-INVICTUS/R012-0014open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1849862026-06-06T12:50:31Z
dc.title.none.fl_str_mv In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
title In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
spellingShingle In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
Agulla, Jesús
Cerebral ischemia
Peri-infarct region
MRI
Theranostics
Drug delivery
title_short In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
title_full In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
title_fullStr In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
title_full_unstemmed In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
title_sort In Vivo Theranostics at the Peri-Infarct Region in Cerebral Ischemia
dc.creator.none.fl_str_mv Agulla, Jesús
Brea, David
Campos, Francisco|||0000-0001-8665-1039
Sobrino, Tomás|||0000-0002-9760-8690
Argibay, Bárbara
Al-Soufi, Wajih
Blanco, Miguel
Castillo, José
Ramos-Cabrer, Pedro|||0000-0003-0368-7031
author Agulla, Jesús
author_facet Agulla, Jesús
Brea, David
Campos, Francisco|||0000-0001-8665-1039
Sobrino, Tomás|||0000-0002-9760-8690
Argibay, Bárbara
Al-Soufi, Wajih
Blanco, Miguel
Castillo, José
Ramos-Cabrer, Pedro|||0000-0003-0368-7031
author_role author
author2 Brea, David
Campos, Francisco|||0000-0001-8665-1039
Sobrino, Tomás|||0000-0002-9760-8690
Argibay, Bárbara
Al-Soufi, Wajih
Blanco, Miguel
Castillo, José
Ramos-Cabrer, Pedro|||0000-0003-0368-7031
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cerebral ischemia
Peri-infarct region
MRI
Theranostics
Drug delivery
topic Cerebral ischemia
Peri-infarct region
MRI
Theranostics
Drug delivery
description The use of theranostics in neurosciences has been rare to date because of the limitations imposed on the free delivery of substances to the brain by the blood-brain barrier. Here we report the development of a theranostic system for the treatment of stroke, a leading cause of death and disability in developed countries. We first performed a series of proteomic, immunoblotting and immunohistological studies to characterize the expression of molecular biomarkers for the so-called peri-infarct tissue, a key region of the brain for stroke treatment. We confirmed that the HSP72 protein is a suitable biomarker for the peri-infarct region, as it is selectively expressed by at-risk tissue for up to 7 days following cerebral ischemia. We also describe the development of anti-HSP72 vectorized stealth immunoliposomes containing imaging probes to make them traceable by conventional imaging techniques (fluorescence and MRI) that were used to encapsulate a therapeutic agent (citicoline) for the treatment of cerebral ischemia. We tested the molecular recognition capabilities of these nano-platforms in vitro together with their diagnostic and therapeutic properties in vivo, in an animal model of cerebral ischemia. Using MRI, we found that 80% of vectorized liposomes were located on the periphery of the ischemic lesion, and animals treated with citicoline encapsulated on these liposomes presented lesion volumes up to 30% smaller than animals treated with free (non-encapsulated) drugs. Our results show the potential of nanotechnology for the development of effective tools for the treatment of neurological diseases.
publishDate 2013
dc.date.none.fl_str_mv 2
2013-01-01
2013
2013-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/184986
https://dx.doi.org/urn:doi:10.7150/thno.7088
url https://ddd.uab.cat/record/184986
https://dx.doi.org/urn:doi:10.7150/thno.7088
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI11-02161
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CP09-00074
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2008-02190
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2011-30517
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RETICS-INVICTUS/R012-0014
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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