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dc.contributor.author | Muniesa Lajara, Carlos | es_ES |
dc.contributor.author | Vicente Vilas, Victor | es_ES |
dc.contributor.author | Quesada Vilar, Manuel | es_ES |
dc.contributor.author | SAEZ-ATIENZAR, SARA | es_ES |
dc.contributor.author | BLESA-BLESA, JOSE RAFAEL | es_ES |
dc.contributor.author | Abasolo, Ibane | es_ES |
dc.contributor.author | Fernández, Yolanda | es_ES |
dc.contributor.author | Botella Asuncion, Pablo | es_ES |
dc.date.accessioned | 2017-07-20T07:31:22Z | |
dc.date.available | 2017-07-20T07:31:22Z | |
dc.date.issued | 2013 | |
dc.identifier.issn | 2046-2069 | |
dc.identifier.uri | http://hdl.handle.net/10251/85514 | |
dc.description.abstract | [EN] We report the design, synthesis, characterization and in vitro testing of a novel nanodrug based on a covalent linking model that allows intracellular controlled release of the pharmaceutical payload. A new synthetic strategy is implemented by direct coupling of as-synthesized (pyridin-2-yldisulfanyl)alkyl carbonate derivatives of camptothecin (CPT) with thiol groups of silica hybrid nanoparticles containing a non-porous core and a mesoporous shell. Upon reaction with thiols in physiological conditions, disulfide bridge cleavage occurs, releasing the naked drug after an intramolecular cyclization mechanism. Additional incorporation of a fluorophore into particles core facilitates imaging at the subcellular level for the monitoring of uptake and delivery. Confocal microscopy experiments in HeLa cervix cancer cells confirms that nanoparticles enter the cells by endocytosis but are able to escape from endo-lysosomes and enter the cytosolic compartment to release their cargo. The incorporation to cells of L-buthionine-sulfoximine, a glutathione inhibitor allows concluding that the intracellular releasing mechanism is mainly driven by the reducing activity of this tripeptide. This camptothecin nanoplatform shows the same cytotoxic activity than the free drug and is clearly superior to those release systems depending on enzymatic hydrolysis (as determined by calculation of the IC50 ratios). | es_ES |
dc.description.sponsorship | This work was financially supported by "Comision Interministerial de Ciencia y Tecnologia" of Spain (projects CSD2009-00050 and MAT2012-39290-C02-02), and grants from CIBER-BBN (NanoMets Intramural Grant) "Fondo de Investigaciones Sanitarias - Instituto de Salud Carlos III" (PI080771) y "Universidad Catolica de Valencia San Vicente Martir" (PI2011-011-010). CM thanks the Spanish "Ministerio de Economia y Competitividad" for a FPU Ph.D. studentship (AP2008-02851). SSA thanks the "Universidad Catolica de Valencia San Vicente Martir" for a Ph.D. studentship. | |
dc.language | Inglés | es_ES |
dc.publisher | Royal Society of Chemistry | es_ES |
dc.relation.ispartof | RSC Advances | es_ES |
dc.rights | Reconocimiento (by) | es_ES |
dc.subject | Mesopourus silica nanoparticles | es_ES |
dc.subject | Drug delivery | es_ES |
dc.subject | Responsive nanoparticles | es_ES |
dc.subject | Carbon nanotubes | es_ES |
dc.subject | Disulfide bonds | es_ES |
dc.subject | Gene delivery | es_ES |
dc.subject | Cancer cells | es_ES |
dc.subject | In vivo | es_ES |
dc.subject | Agents | es_ES |
dc.subject | Folate | es_ES |
dc.title | Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin | es_ES |
dc.type | Artículo | es_ES |
dc.identifier.doi | 10.1039/c3ra41404c | |
dc.relation.projectID | info:eu-repo/grantAgreement/MICINN//CSD2009-00050/ES/Desarrollo de catalizadores más eficientes para el diseño de procesos químicos sostenibles y produccion limpia de energia/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/UCV//PI2011-011-010/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ISCIII//PI080771/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/MINECO//MAT2012-39290-C02-02/ES/NUEVAS CUBIERTAS BIOCOMPATIBLES Y ANTIINFLAMATORIAS PARA ELECTRODOS NEURALES/ | |
dc.rights.accessRights | Abierto | es_ES |
dc.contributor.affiliation | Universitat Politècnica de València. Instituto Universitario Mixto de Tecnología Química - Institut Universitari Mixt de Tecnologia Química | es_ES |
dc.description.bibliographicCitation | Muniesa Lajara, C.; Vicente Vilas, V.; Quesada Vilar, M.; Saez-Atienzar, S.; Blesa-Blesa, JR.; Abasolo, I.; Fernández, Y.... (2013). Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin. RSC Advances. 3(35):15121-15131. https://doi.org/10.1039/c3ra41404c | es_ES |
dc.description.accrualMethod | S | es_ES |
dc.relation.publisherversion | http://doi.org/10.1039/c3ra41404c | es_ES |
dc.description.upvformatpinicio | 15121 | es_ES |
dc.description.upvformatpfin | 15131 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | es_ES |
dc.description.volume | 3 | es_ES |
dc.description.issue | 35 | es_ES |
dc.relation.senia | 260240 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Universidad Católica de Valencia San Vicente Mártir | |
dc.contributor.funder | Ministerio de Economía y Competitividad | |
dc.contributor.funder | Ministerio de Ciencia e Innovación |