epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells

[EN] Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Ac alpha interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumor cells. Very recently, a short peptide (C9h) known to disrupt caspase-9/P...

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Autores: De La Torre-Paredes, Cristina, Domínguez-Berrocal, L., Bravo,J., Murguía, Jose R.|||0000-0001-9364-4603, Marcos Martínez, María Dolores|||0000-0001-7079-8589, Martínez-Máñez, Ramón|||0000-0001-5873-9674, Sancenón Galarza, Félix|||0000-0002-5205-7135
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/141963
Acceso en línea:https://riunet.upv.es/handle/10251/141963
Access Level:acceso abierto
Palabra clave:Apoptosis
Caspase-9
Drug delivery
Gated nanoparticles
Peptides
QUIMICA INORGANICA
QUIMICA ANALITICA
BIOQUIMICA Y BIOLOGIA MOLECULAR
QUIMICA ORGANICA
id ES_f1dacb977d1c0cfbe76191f4bef29ffc
oai_identifier_str oai:riunet.upv.es:10251/141963
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
title epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
spellingShingle epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
De La Torre-Paredes, Cristina
Apoptosis
Caspase-9
Drug delivery
Gated nanoparticles
Peptides
QUIMICA INORGANICA
QUIMICA ANALITICA
BIOQUIMICA Y BIOLOGIA MOLECULAR
QUIMICA ORGANICA
title_short epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
title_full epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
title_fullStr epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
title_full_unstemmed epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
title_sort epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells
dc.creator.none.fl_str_mv De La Torre-Paredes, Cristina
Domínguez-Berrocal, L.
Bravo,J.
Murguía, Jose R.|||0000-0001-9364-4603
Marcos Martínez, María Dolores|||0000-0001-7079-8589
Martínez-Máñez, Ramón|||0000-0001-5873-9674
Sancenón Galarza, Félix|||0000-0002-5205-7135
author De La Torre-Paredes, Cristina
author_facet De La Torre-Paredes, Cristina
Domínguez-Berrocal, L.
Bravo,J.
Murguía, Jose R.|||0000-0001-9364-4603
Marcos Martínez, María Dolores|||0000-0001-7079-8589
Martínez-Máñez, Ramón|||0000-0001-5873-9674
Sancenón Galarza, Félix|||0000-0002-5205-7135
author_role author
author2 Domínguez-Berrocal, L.
Bravo,J.
Murguía, Jose R.|||0000-0001-9364-4603
Marcos Martínez, María Dolores|||0000-0001-7079-8589
Martínez-Máñez, Ramón|||0000-0001-5873-9674
Sancenón Galarza, Félix|||0000-0002-5205-7135
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biotecnología
Escuela Técnica Superior de Ingeniería Aeroespacial y Diseño Industrial
Departamento de Química
Escuela Técnica Superior de Ingeniería Industrial
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico
Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural
Generalitat Valenciana
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina
Ministerio de Ciencia e Innovación
Ministerio de Economía y Competitividad
European Regional Development Fund
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Apoptosis
Caspase-9
Drug delivery
Gated nanoparticles
Peptides
QUIMICA INORGANICA
QUIMICA ANALITICA
BIOQUIMICA Y BIOLOGIA MOLECULAR
QUIMICA ORGANICA
topic Apoptosis
Caspase-9
Drug delivery
Gated nanoparticles
Peptides
QUIMICA INORGANICA
QUIMICA ANALITICA
BIOQUIMICA Y BIOLOGIA MOLECULAR
QUIMICA ORGANICA
description [EN] Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Ac alpha interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumor cells. Very recently, a short peptide (C9h) known to disrupt caspase-9/PP2Ac alpha interaction with subsequent apoptosis induction was described. Here, we prepared two sets of mesoporous silica nanoparticles loaded with safraninO (S2) or with C9h peptide (S4) and functionalized with epsilon-polylysine as capping unit. Aqueous suspensions of both nanoparticles showed negligible cargo release whereas in the presence of pronase, a marked delivery of safraninO or C9h was observed. Confocal microscopy studies carried out with HeLa cells indicated that both materials were internalized and were able to release their entrapped cargos. Besides, a marked decrease in HeLa cell viability (ca. 50%) was observed when treated with C9h-loaded S4 nanoparticles. Moreover, S4 provides peptide protection from degradation additionally allowing for a dose reduction to observe an apoptotic effect when compared with C9h alone or in combination with a cell-penetrating peptide (i.e., Mut3DPT-C9h). Flow cytometry studies, by means of Annexin V-FITC staining, showed the activation of apoptotic pathways in HeLa as a consequence of S4 internalization, release of C9h peptide and disruption of caspase-9/PP2Ac alpha interaction.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-02-01
dc.type.none.fl_str_mv journal 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://riunet.upv.es/handle/10251/141963
url https://riunet.upv.es/handle/10251/141963
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 SAF2012-31405 ESTRUCTURA Y FUNCION DE COMPLEJOS INVOLUCRADOS EN CANCER, METASTASIS Y APOPTOSIS
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 SAF2015-67077-R ESTRUCTURA DE COMPONENTES DE LA VIA DE BIOGENESIS DEL RIBOSOMA Y DISRUPCION DEL PROCESAMIENTO DEL RNA RIBOSOMICO COMO TERAPIA CONTRA EL CANCER
Generalitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2012%2F061
Generalitat Valenciana https://doi.org/10.13039/501100003359 PROMETEOII%2F2014%2F047 Nuevas aproximaciones para el diseño de materiales de liberación controlada y la detección de compuestos peligrosos
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 AGL2015-70235-C2-2-R DESARROLLO DE SISTEMAS HIBRIDOS CON OPTIMIZACION DEL ANCLADO DE BIOMOLECULAS Y DISEÑADOS CON PROPIEDADES DE ENCAPSULACION Y LIBERACION CONTROLADA MEJORADAS
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 MAT2015-64139-C4-1-R NANOMATERIALES INTELIGENTES, SONDAS Y DISPOSITIVOS PARA EL DESARROLLO INTEGRADO DE NUEVAS HERRAMIENTAS APLICADAS AL CAMPO BIOMEDICO
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reserva de todos los derechos
http://rightsstatements.org/vocab/InC/1.0/
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
Reserva de todos los derechos
http://rightsstatements.org/vocab/InC/1.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
instname:Universitat Politècnica de València (UPV)
instname_str Universitat Politècnica de València (UPV)
reponame_str RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
collection RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer CellsDe La Torre-Paredes, CristinaDomínguez-Berrocal, L.Bravo,J.Murguía, Jose R.|||0000-0001-9364-4603Marcos Martínez, María Dolores|||0000-0001-7079-8589Martínez-Máñez, Ramón|||0000-0001-5873-9674Sancenón Galarza, Félix|||0000-0002-5205-7135ApoptosisCaspase-9Drug deliveryGated nanoparticlesPeptidesQUIMICA INORGANICAQUIMICA ANALITICABIOQUIMICA Y BIOLOGIA MOLECULARQUIMICA ORGANICA[EN] Apoptotic signaling pathways are altered in numerous pathologies such as cancer. In this scenario, caspase-9/PP2Ac alpha interaction constitutes a key target with pharmacological interest to re-establish apoptosis in tumor cells. Very recently, a short peptide (C9h) known to disrupt caspase-9/PP2Ac alpha interaction with subsequent apoptosis induction was described. Here, we prepared two sets of mesoporous silica nanoparticles loaded with safraninO (S2) or with C9h peptide (S4) and functionalized with epsilon-polylysine as capping unit. Aqueous suspensions of both nanoparticles showed negligible cargo release whereas in the presence of pronase, a marked delivery of safraninO or C9h was observed. Confocal microscopy studies carried out with HeLa cells indicated that both materials were internalized and were able to release their entrapped cargos. Besides, a marked decrease in HeLa cell viability (ca. 50%) was observed when treated with C9h-loaded S4 nanoparticles. Moreover, S4 provides peptide protection from degradation additionally allowing for a dose reduction to observe an apoptotic effect when compared with C9h alone or in combination with a cell-penetrating peptide (i.e., Mut3DPT-C9h). Flow cytometry studies, by means of Annexin V-FITC staining, showed the activation of apoptotic pathways in HeLa as a consequence of S4 internalization, release of C9h peptide and disruption of caspase-9/PP2Ac alpha interaction.The authors wish to express their gratitude to the Spanish government (Projects MAT2015-64139-C4-1, SAF2012-31405, SAF2015-67077-R, AGL2015-70235-C2-2-R (MINECO/FEDER)), the Generalitat Valencia (Projects PROMETEOII/2014/047, PROMETEO/2012/061) and the CIBER-BBN for their support. C.T. is grateful to the Spanish Ministry of Science and Innovation for her Ph.D. fellowship.John Wiley & SonsDepartamento de BiotecnologíaEscuela Técnica Superior de Ingeniería Aeroespacial y Diseño IndustrialDepartamento de QuímicaEscuela Técnica Superior de Ingeniería IndustrialInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo TecnológicoEscuela Técnica Superior de Ingeniería Agronómica y del Medio NaturalGeneralitat ValencianaCentro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y NanomedicinaMinisterio de Ciencia e InnovaciónMinisterio de Economía y CompetitividadEuropean Regional Development FundRepositorio Institucional de la Universitat Politècnica de València Riunet20182018-02-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://riunet.upv.es/handle/10251/141963reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 SAF2012-31405 ESTRUCTURA Y FUNCION DE COMPLEJOS INVOLUCRADOS EN CANCER, METASTASIS Y APOPTOSISMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 SAF2015-67077-R ESTRUCTURA DE COMPONENTES DE LA VIA DE BIOGENESIS DEL RIBOSOMA Y DISRUPCION DEL PROCESAMIENTO DEL RNA RIBOSOMICO COMO TERAPIA CONTRA EL CANCERGeneralitat Valenciana https://doi.org/10.13039/501100003359 PROMETEO%2F2012%2F061Generalitat Valenciana https://doi.org/10.13039/501100003359 PROMETEOII%2F2014%2F047 Nuevas aproximaciones para el diseño de materiales de liberación controlada y la detección de compuestos peligrososMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 AGL2015-70235-C2-2-R DESARROLLO DE SISTEMAS HIBRIDOS CON OPTIMIZACION DEL ANCLADO DE BIOMOLECULAS Y DISEÑADOS CON PROPIEDADES DE ENCAPSULACION Y LIBERACION CONTROLADA MEJORADASMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 MAT2015-64139-C4-1-R NANOMATERIALES INTELIGENTES, SONDAS Y DISPOSITIVOS PARA EL DESARROLLO INTEGRADO DE NUEVAS HERRAMIENTAS APLICADAS AL CAMPO BIOMEDICOopen accesshttp://purl.org/coar/access_right/c_abf2Reserva de todos los derechoshttp://rightsstatements.org/vocab/InC/1.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/1419632026-06-13T07:49:27Z
score 15,301603

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