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

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

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dc.contributor.author De La Torre-Paredes, Cristina es_ES
dc.contributor.author Domínguez-Berrocal, L. es_ES
dc.contributor.author Murguía, Jose R. es_ES
dc.contributor.author Marcos Martínez, María Dolores es_ES
dc.contributor.author Martínez-Máñez, Ramón es_ES
dc.contributor.author Bravo,J. es_ES
dc.contributor.author Sancenón Galarza, Félix es_ES
dc.date.accessioned 2020-04-29T07:05:00Z
dc.date.available 2020-04-29T07:05:00Z
dc.date.issued 2018-02 es_ES
dc.identifier.issn 0947-6539 es_ES
dc.identifier.uri http://hdl.handle.net/10251/141963
dc.description.abstract [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. es_ES
dc.description.sponsorship 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. es_ES
dc.language Inglés es_ES
dc.publisher John Wiley & Sons es_ES
dc.relation.ispartof Chemistry - A European Journal es_ES
dc.rights Reserva de todos los derechos es_ES
dc.subject Apoptosis es_ES
dc.subject Caspase-9 es_ES
dc.subject Drug delivery es_ES
dc.subject Gated nanoparticles es_ES
dc.subject Peptides es_ES
dc.subject.classification QUIMICA INORGANICA es_ES
dc.subject.classification QUIMICA ANALITICA es_ES
dc.subject.classification BIOQUIMICA Y BIOLOGIA MOLECULAR es_ES
dc.subject.classification QUIMICA ORGANICA es_ES
dc.title epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1002/chem.201704161 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//SAF2012-31405/ES/ESTRUCTURA Y FUNCION DE COMPLEJOS INVOLUCRADOS EN CANCER, METASTASIS Y APOPTOSIS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//SAF2015-67077-R/ES/ESTRUCTURA DE COMPONENTES DE LA VIA DE BIOGENESIS DEL RIBOSOMA Y DISRUPCION DEL PROCESAMIENTO DEL RNA RIBOSOMICO COMO TERAPIA CONTRA EL CANCER/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEO%2F2012%2F061/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEOII%2F2014%2F047/ES/Nuevas aproximaciones para el diseño de materiales de liberación controlada y la detección de compuestos peligrosos/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//AGL2015-70235-C2-2-R/ES/DESARROLLO DE SISTEMAS HIBRIDOS CON OPTIMIZACION DEL ANCLADO DE BIOMOLECULAS Y DISEÑADOS CON PROPIEDADES DE ENCAPSULACION Y LIBERACION CONTROLADA MEJORADAS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//MAT2015-64139-C4-1-R/ES/NANOMATERIALES INTELIGENTES, SONDAS Y DISPOSITIVOS PARA EL DESARROLLO INTEGRADO DE NUEVAS HERRAMIENTAS APLICADAS AL CAMPO BIOMEDICO/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Química - Departament de Química es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia es_ES
dc.description.bibliographicCitation De La Torre-Paredes, C.; Domínguez-Berrocal, L.; Murguía, JR.; Marcos Martínez, MD.; Martínez-Máñez, R.; Bravo, J.; Sancenón Galarza, F. (2018). epsilon-Polylysine-Capped Mesoporous Silica Nanoparticles as Carrier of the C9h Peptide to Induce Apoptosis in Cancer Cells. Chemistry - A European Journal. 24(8):1890-1897. https://doi.org/10.1002/chem.201704161 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1002/chem.201704161 es_ES
dc.description.upvformatpinicio 1890 es_ES
dc.description.upvformatpfin 1897 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 24 es_ES
dc.description.issue 8 es_ES
dc.identifier.pmid 29193344 es_ES
dc.relation.pasarela S\354089 es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina es_ES
dc.contributor.funder Ministerio de Ciencia e Innovación es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES
dc.contributor.funder European Regional Development Fund es_ES
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