In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-load...

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Autores: Nogueira, Daniele Rubert, Tavano, Lorena, Mitjans, Montserrat, Pérez, Lourdes, Infante, María Rosa, Vinardell, M. Pilar
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/131389
Acceso en línea:http://hdl.handle.net/10261/131389
Access Level:acceso abierto
Palabra clave:Chitosan nanoparticles
Cytotoxicity
Intracellular drug delivery
Methotrexate
PH-sensitivity
Lysine-based surfactant
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spelling In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticlesNogueira, Daniele RubertTavano, LorenaMitjans, MontserratPérez, LourdesInfante, María RosaVinardell, M. PilarChitosan nanoparticlesCytotoxicityIntracellular drug deliveryMethotrexatePH-sensitivityLysine-based surfactantNanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from Nα,Nε-dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy. © 2013 Elsevier LtdThis research was supported by Projects CTQ2009-14151-C02-02 and CTQ2009-14151-C02-01 of the Ministerio de Ciencia e Innovación (Spain). Daniele Rubert Nogueira holds a PhD grant from MAEC-AECID (Spain).Peer reviewedElsevierMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201620162013info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/131389reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.biomaterials.2013.01.005Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1313892026-05-22T06:33:51Z
dc.title.none.fl_str_mv In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
title In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
spellingShingle In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
Nogueira, Daniele Rubert
Chitosan nanoparticles
Cytotoxicity
Intracellular drug delivery
Methotrexate
PH-sensitivity
Lysine-based surfactant
title_short In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
title_full In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
title_fullStr In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
title_full_unstemmed In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
title_sort In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles
dc.creator.none.fl_str_mv Nogueira, Daniele Rubert
Tavano, Lorena
Mitjans, Montserrat
Pérez, Lourdes
Infante, María Rosa
Vinardell, M. Pilar
author Nogueira, Daniele Rubert
author_facet Nogueira, Daniele Rubert
Tavano, Lorena
Mitjans, Montserrat
Pérez, Lourdes
Infante, María Rosa
Vinardell, M. Pilar
author_role author
author2 Tavano, Lorena
Mitjans, Montserrat
Pérez, Lourdes
Infante, María Rosa
Vinardell, M. Pilar
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Chitosan nanoparticles
Cytotoxicity
Intracellular drug delivery
Methotrexate
PH-sensitivity
Lysine-based surfactant
topic Chitosan nanoparticles
Cytotoxicity
Intracellular drug delivery
Methotrexate
PH-sensitivity
Lysine-based surfactant
description Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from Nα,Nε-dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy. © 2013 Elsevier Ltd
publishDate 2013
dc.date.none.fl_str_mv 2013
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/131389
url http://hdl.handle.net/10261/131389
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.biomaterials.2013.01.005
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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