Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.

[EN] We synthesized a non-viral delivery system (f-CNH3) for small interfering RNA (siRNA) by anchoring a fourth-generation polyamidoamine dendrimer (G4-PAMAM) to carbon nanohorns (CNHs). Using this new compound, we delivered a specific siRNA designed to knockdown cofilin-1, a key protein in the reg...

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Autores: Pérez-Martínez, Francisco C., Carrión, Blanca, Rubio, Noelia, Herrero, Maria A., Vázquez, Ester, Ceña, Valentín, Lucío, María Isabel|||0000-0001-7404-352X
Tipo de recurso: artículo
Fecha de publicación:2012
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:10251/201989
Acceso en línea:https://riunet.upv.es/handle/10251/201989
Access Level:acceso abierto
Palabra clave:Dendrimer
Gene therapy
Nanoparticle
SiRNA
Prostate cancer
QUIMICA ANALITICA
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spelling Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.Pérez-Martínez, Francisco C.Carrión, BlancaRubio, NoeliaHerrero, Maria A.Vázquez, EsterCeña, ValentínLucío, María Isabel|||0000-0001-7404-352XDendrimerGene therapyNanoparticleSiRNAProstate cancerQUIMICA ANALITICA[EN] We synthesized a non-viral delivery system (f-CNH3) for small interfering RNA (siRNA) by anchoring a fourth-generation polyamidoamine dendrimer (G4-PAMAM) to carbon nanohorns (CNHs). Using this new compound, we delivered a specific siRNA designed to knockdown cofilin-1, a key protein in the regulation of cellular cytoskeleton, to human prostate cancer (PCa) cells. The carbon nanohorn (CNH) derivative was able to bind siRNA and release it in the presence of an excess of the polyanion heparin. Moreover, this hybrid nanomaterial protected the siRNA from RNAse-mediated degradation. Synthetic siRNA delivered to PCa cells by f-CNH3 decreased the cofilin-1 mRNA and protein levels to about 20% of control values. Docetaxel, the drug of choice for the treatment of PCa, produced a concentration-dependent activation of caspase-3, an increase in cell death assessed by lactate dehydrogenase release to the culture medium, cell cycle arrest and inhibition of tumor cell proliferation. All of these toxic effects were potentiated when cofilin-1 was down regulated in these cells by a siRNA delivered by the nanoparticle. This suggests that knocking down certain proteins involved in cancer cell survival and/or proliferation may potentiate the cytotoxic actions of anticancer drugs and it might be a new therapeutic approach to treat tumors.F.C.P-M. and B.C. are recipients of Torres Quevedo contracts from Ministerio de Ciencia e Innovacion (Spain) and NanoDrugs, S.L. This work has been supported, in part, by grants BFU2011-30161-C02-01 from Ministerio de Ciencia e Innovacion; PII1I09-0163-4002 and POII10-0274-3182 from Consejeria de Educacion, JCCM to V.C.ElsevierDepartamento de QuímicaEscuela Técnica Superior de Ingeniería IndustrialInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo TecnológicoEscuela Técnica Superior de Ingeniería Agronómica y del Medio NaturalMinisterio de Ciencia e InnovaciónJunta de Comunidades de Castilla-La ManchaRepositorio Institucional de la Universitat Politècnica de València Riunet20122012-11-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://riunet.upv.es/handle/10251/201989reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengJunta de Comunidades de Castilla-La Mancha https://doi.org/10.13039/501100011698 PII1I09-0163-4002 Papel De La Proteína P53 En La Activación Mitocondrial Durante Los Procesos ExcitotóxicosJunta de Comunidades de Castilla-La Mancha https://doi.org/10.13039/501100011698 POII10-0274-3182 Dendrímeros como base de la terapia génica en la terapéutica de la osteopenia asociada a la diabetes mellitusMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 BFU2011-30161-C02-01 NANOPARTICULAS NO VIRALES COMO VECTORES PARA SIRNA EN CELULAS TUMORALES Y NEURONASopen accesshttp://purl.org/coar/access_right/c_abf2Reconocimiento - No comercial - Sin obra derivada (by-nc-nd) http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:riunet.upv.es:10251/2019892026-06-13T07:49:27Z
dc.title.none.fl_str_mv Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
title Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
spellingShingle Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
Pérez-Martínez, Francisco C.
Dendrimer
Gene therapy
Nanoparticle
SiRNA
Prostate cancer
QUIMICA ANALITICA
title_short Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
title_full Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
title_fullStr Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
title_full_unstemmed Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
title_sort Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorns delivered siRNA.
dc.creator.none.fl_str_mv Pérez-Martínez, Francisco C.
Carrión, Blanca
Rubio, Noelia
Herrero, Maria A.
Vázquez, Ester
Ceña, Valentín
Lucío, María Isabel|||0000-0001-7404-352X
author Pérez-Martínez, Francisco C.
author_facet Pérez-Martínez, Francisco C.
Carrión, Blanca
Rubio, Noelia
Herrero, Maria A.
Vázquez, Ester
Ceña, Valentín
Lucío, María Isabel|||0000-0001-7404-352X
author_role author
author2 Carrión, Blanca
Rubio, Noelia
Herrero, Maria A.
Vázquez, Ester
Ceña, Valentín
Lucío, María Isabel|||0000-0001-7404-352X
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv 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
Ministerio de Ciencia e Innovación
Junta de Comunidades de Castilla-La Mancha
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Dendrimer
Gene therapy
Nanoparticle
SiRNA
Prostate cancer
QUIMICA ANALITICA
topic Dendrimer
Gene therapy
Nanoparticle
SiRNA
Prostate cancer
QUIMICA ANALITICA
description [EN] We synthesized a non-viral delivery system (f-CNH3) for small interfering RNA (siRNA) by anchoring a fourth-generation polyamidoamine dendrimer (G4-PAMAM) to carbon nanohorns (CNHs). Using this new compound, we delivered a specific siRNA designed to knockdown cofilin-1, a key protein in the regulation of cellular cytoskeleton, to human prostate cancer (PCa) cells. The carbon nanohorn (CNH) derivative was able to bind siRNA and release it in the presence of an excess of the polyanion heparin. Moreover, this hybrid nanomaterial protected the siRNA from RNAse-mediated degradation. Synthetic siRNA delivered to PCa cells by f-CNH3 decreased the cofilin-1 mRNA and protein levels to about 20% of control values. Docetaxel, the drug of choice for the treatment of PCa, produced a concentration-dependent activation of caspase-3, an increase in cell death assessed by lactate dehydrogenase release to the culture medium, cell cycle arrest and inhibition of tumor cell proliferation. All of these toxic effects were potentiated when cofilin-1 was down regulated in these cells by a siRNA delivered by the nanoparticle. This suggests that knocking down certain proteins involved in cancer cell survival and/or proliferation may potentiate the cytotoxic actions of anticancer drugs and it might be a new therapeutic approach to treat tumors.
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-11-01
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/10251/201989
url https://riunet.upv.es/handle/10251/201989
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Junta de Comunidades de Castilla-La Mancha https://doi.org/10.13039/501100011698 PII1I09-0163-4002 Papel De La Proteína P53 En La Activación Mitocondrial Durante Los Procesos Excitotóxicos
Junta de Comunidades de Castilla-La Mancha https://doi.org/10.13039/501100011698 POII10-0274-3182 Dendrímeros como base de la terapia génica en la terapéutica de la osteopenia asociada a la diabetes mellitus
Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 BFU2011-30161-C02-01 NANOPARTICULAS NO VIRALES COMO VECTORES PARA SIRNA EN CELULAS TUMORALES Y NEURONAS
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Reconocimiento - No comercial - Sin obra derivada (by-nc-nd)
http://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
Reconocimiento - No comercial - Sin obra derivada (by-nc-nd)
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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score 15.300719

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