Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery

[EN] Hypoxia, i.e., low oxygen concentration at the tissue level, is a common feature of most solid tumors, and is responsible for their enhanced aggressiveness and resistance to chemotherapy, radiotherapy and photodynamic therapy. Hypoxic microenvironments are also characterized by the overexpressi...

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Autores: Barros, Mariana, Sáez José A., Arroyo, Pau, Ros-Lis, J. Vicente, Garrido, M. Dolores, Terencio, M. Carmen, Montesinos, M. Carmen, Gaviña, Pablo, Martínez-Máñez, Ramón|||0000-0001-5873-9674
Tipo de recurso: artículo
Fecha de publicación:2025
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:10251/220649
Acceso en línea:https://riunet.upv.es/handle/10251/220649
Access Level:acceso abierto
Palabra clave:Hypoxia-responsive
Nitroreductase
Doxorubicin
Controlled delivery
Mesoporous silica nanocarriers
Self-immolative gatekeepers
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
title Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
spellingShingle Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
Barros, Mariana
Hypoxia-responsive
Nitroreductase
Doxorubicin
Controlled delivery
Mesoporous silica nanocarriers
Self-immolative gatekeepers
title_short Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
title_full Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
title_fullStr Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
title_full_unstemmed Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
title_sort Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug delivery
dc.creator.none.fl_str_mv Barros, Mariana
Sáez José A.
Arroyo, Pau
Ros-Lis, J. Vicente
Garrido, M. Dolores
Terencio, M. Carmen
Montesinos, M. Carmen
Gaviña, Pablo
Martínez-Máñez, Ramón|||0000-0001-5873-9674
author Barros, Mariana
author_facet Barros, Mariana
Sáez José A.
Arroyo, Pau
Ros-Lis, J. Vicente
Garrido, M. Dolores
Terencio, M. Carmen
Montesinos, M. Carmen
Gaviña, Pablo
Martínez-Máñez, Ramón|||0000-0001-5873-9674
author_role author
author2 Sáez José A.
Arroyo, Pau
Ros-Lis, J. Vicente
Garrido, M. Dolores
Terencio, M. Carmen
Montesinos, M. Carmen
Gaviña, Pablo
Martínez-Máñez, Ramón|||0000-0001-5873-9674
author2_role author
author
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
Generalitat Valenciana
Agencia Estatal de Investigación
European Regional Development Fund
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Hypoxia-responsive
Nitroreductase
Doxorubicin
Controlled delivery
Mesoporous silica nanocarriers
Self-immolative gatekeepers
topic Hypoxia-responsive
Nitroreductase
Doxorubicin
Controlled delivery
Mesoporous silica nanocarriers
Self-immolative gatekeepers
description [EN] Hypoxia, i.e., low oxygen concentration at the tissue level, is a common feature of most solid tumors, and is responsible for their enhanced aggressiveness and resistance to chemotherapy, radiotherapy and photodynamic therapy. Hypoxic microenvironments are also characterized by the overexpression of various reductase enzymes such as nitroreductases. Herein, we report a hypoxia-responsive hybrid nanomaterial consisting of mesoporous silica nanoparticles, loaded with the chemotherapy drug doxorubicin, and functionalized on their surface with a self-immolative gatekeeper responsive to nitroreductases, for the controlled release of the cargo. Thus, under bioreductive conditions, elicited by the presence of nitroreductase and NADH, the reduction of the nitroaromatic containing molecular gate induces a self-immolative elimination leading to the disintegration of the gatekeeper and the delivery of the doxorubicin from inside the pores. The nitroreductase-responsive nanocarrier has been tested in vitro with A549 cells, that are known to express nitroreductase, to demonstrate its effectiveness as drug carrier for doxorubicin release, showing great potential for the treatment of hypoxic tumors.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-03-15
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/10251/220649
url https://riunet.upv.es/handle/10251/220649
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126304OB-C41 NUEVOS MATERIALES Y SONDAS PARA EL RECONOCIMIENTO, LIBERACION DE FARMACOS, NANOMOTORES Y COMUNICACION
Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126304OB-C42 QUIMIOSENSORES Y MATERIALES INTELIGENTES PARA LA DETECCION DE DROGAS Y EL TRATAMIENTO%2FIMAGEN DE TUMORES HIPOXICOS
Agencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126304OB-C43 SINTESIS Y APLICACIONES SELECCIONADAS DE NUEVOS NANOMATERIALES Y NANOCOMPUESTOS POROSOS MULTIFUNCIONALES
Generalitat Valenciana https://doi.org/10.13039/501100003359 CIAICO%2F2022%2F146
Generalitat Valenciana https://doi.org/10.13039/501100003359 CIPROM%2F2021%2F007
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
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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spelling Nitroreductase-responsive gated mesoporous silica nanocarriers for hypoxia-targeted drug deliveryBarros, MarianaSáez José A.Arroyo, PauRos-Lis, J. VicenteGarrido, M. DoloresTerencio, M. CarmenMontesinos, M. CarmenGaviña, PabloMartínez-Máñez, Ramón|||0000-0001-5873-9674Hypoxia-responsiveNitroreductaseDoxorubicinControlled deliveryMesoporous silica nanocarriersSelf-immolative gatekeepers[EN] Hypoxia, i.e., low oxygen concentration at the tissue level, is a common feature of most solid tumors, and is responsible for their enhanced aggressiveness and resistance to chemotherapy, radiotherapy and photodynamic therapy. Hypoxic microenvironments are also characterized by the overexpression of various reductase enzymes such as nitroreductases. Herein, we report a hypoxia-responsive hybrid nanomaterial consisting of mesoporous silica nanoparticles, loaded with the chemotherapy drug doxorubicin, and functionalized on their surface with a self-immolative gatekeeper responsive to nitroreductases, for the controlled release of the cargo. Thus, under bioreductive conditions, elicited by the presence of nitroreductase and NADH, the reduction of the nitroaromatic containing molecular gate induces a self-immolative elimination leading to the disintegration of the gatekeeper and the delivery of the doxorubicin from inside the pores. The nitroreductase-responsive nanocarrier has been tested in vitro with A549 cells, that are known to express nitroreductase, to demonstrate its effectiveness as drug carrier for doxorubicin release, showing great potential for the treatment of hypoxic tumors.We thank the Spanish Government for grants PID2021-126304OB-C41, PID2021-126304OB-C42, and PID2021-126304OB-C43, funded by MCIN/AEI/10.13039/501100011033/and by European Regional Development Fund-A way of making Europe, EU. We also acknowledge the Generalitat Valenciana (Conselleria de Educacion, Universidades y Empleo) for grants CIAICO/2022/146 and CIPROM/2021/007. SCSIE (Universidad de Valencia) is gratefully acknowledged for all the equipment employed. NMR spectra were registered at the U26 facility of ICTS "NAMBIOSIS" at the Universitat de Valencia.r C41, PID2021-126304OB-C42, and PID2021-126304OB-C43, funded by MCIN/AEI/10.13039/501100011033/and by European Regional Development Fund-A way of making Europe, EU. We also acknowledge the Generalitat Valenciana (Conselleria de Educacio<acute accent>n, Universidades y Empleo) for grants CIAICO/2022/146 and CIPROM/2021/007. SCSIE (Universidad de Valencia) is gratefully acknowledged for all the equipment employed. NMR spectra were registered at the U26 facility of ICTS "NAMBIOSIS" at the Universitat de Vale`ncia.ElsevierDepartamento de QuímicaEscuela Técnica Superior de Ingeniería IndustrialInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo TecnológicoGeneralitat ValencianaAgencia Estatal de InvestigaciónEuropean Regional Development FundRepositorio Institucional de la Universitat Politècnica de València Riunet20252025-03-15journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/220649reponame:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valénciainstname:Universitat Politècnica de València (UPV)InglésengAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126304OB-C41 NUEVOS MATERIALES Y SONDAS PARA EL RECONOCIMIENTO, LIBERACION DE FARMACOS, NANOMOTORES Y COMUNICACIONAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126304OB-C42 QUIMIOSENSORES Y MATERIALES INTELIGENTES PARA LA DETECCION DE DROGAS Y EL TRATAMIENTO%2FIMAGEN DE TUMORES HIPOXICOSAgencia Estatal de Investigación http://dx.doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023 PID2021-126304OB-C43 SINTESIS Y APLICACIONES SELECCIONADAS DE NUEVOS NANOMATERIALES Y NANOCOMPUESTOS POROSOS MULTIFUNCIONALESGeneralitat Valenciana https://doi.org/10.13039/501100003359 CIAICO%2F2022%2F146Generalitat Valenciana https://doi.org/10.13039/501100003359 CIPROM%2F2021%2F007open 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:10251/2206492026-06-13T07:49:27Z
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