A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells

[EN] Cellular senescence is implicated in the occurrence and progression of multiple age-related disorders. In this context, the selective elimination of senescent cells, senolysis, has emerged as an effective therapeu- tic strategy. However, the heterogeneous senescent phenotype hinders the discove...

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Autores: Escriche-Navarro, Blanca, Garrido-García, Eva María, Sancenón Galarza, Félix|||0000-0002-5205-7135, García-Fernández, Alba|||0000-0002-8416-1674, Martínez-Máñez, Ramón|||0000-0001-5873-9674
Tipo de recurso: artículo
Fecha de publicación:2024
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:10251/214710
Acceso en línea:https://riunet.upv.es/handle/10251/214710
Access Level:acceso abierto
Palabra clave:Matrix metalloproteinase-3
Mesoporous silica nanoparticles
Senescence
Navitoclax
QUIMICA ORGANICA
QUIMICA INORGANICA
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oai_identifier_str oai:riunet.upv.es:10251/214710
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
title A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
spellingShingle A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
Escriche-Navarro, Blanca
Matrix metalloproteinase-3
Mesoporous silica nanoparticles
Senescence
Navitoclax
QUIMICA ORGANICA
QUIMICA INORGANICA
title_short A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
title_full A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
title_fullStr A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
title_full_unstemmed A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
title_sort A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cells
dc.creator.none.fl_str_mv Escriche-Navarro, Blanca
Garrido-García, Eva María
Sancenón Galarza, Félix|||0000-0002-5205-7135
García-Fernández, Alba|||0000-0002-8416-1674
Martínez-Máñez, Ramón|||0000-0001-5873-9674
author Escriche-Navarro, Blanca
author_facet Escriche-Navarro, Blanca
Garrido-García, Eva María
Sancenón Galarza, Félix|||0000-0002-5205-7135
García-Fernández, Alba|||0000-0002-8416-1674
Martínez-Máñez, Ramón|||0000-0001-5873-9674
author_role author
author2 Garrido-García, Eva María
Sancenón Galarza, Félix|||0000-0002-5205-7135
García-Fernández, Alba|||0000-0002-8416-1674
Martínez-Máñez, Ramón|||0000-0001-5873-9674
author2_role 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
European Research Council
Ministerio de Universidades
Instituto de Salud Carlos III
Agencia Estatal de Investigación
Universitat Politècnica de València
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Matrix metalloproteinase-3
Mesoporous silica nanoparticles
Senescence
Navitoclax
QUIMICA ORGANICA
QUIMICA INORGANICA
topic Matrix metalloproteinase-3
Mesoporous silica nanoparticles
Senescence
Navitoclax
QUIMICA ORGANICA
QUIMICA INORGANICA
description [EN] Cellular senescence is implicated in the occurrence and progression of multiple age-related disorders. In this context, the selective elimination of senescent cells, senolysis, has emerged as an effective therapeu- tic strategy. However, the heterogeneous senescent phenotype hinders the discovery of a universal and robust senescence biomarker that limits the effective of senolytic with off-target toxic effects. Therefore, the development of more selective strategies represents a promising approach to increase the specificity of senolytic therapy. In this study, we have developed an innovative nanodevice for the selective elimi- nation of senescent cells (SCs) based on the specific enzymatic activity of the senescent secretome. The results revealed that when senescence is induced in proliferating WI-38 by ionizing radiation (IR), the cells secrete high levels of matrix metalloproteinase-3 (MMP-3). Based on this result, mesoporous silica nanoparticles (MSNs) were loaded with the senolytic navitoclax (Nav) and coated with a specific peptide which is substrate of MMP-3 (NPs(Nav)@MMP-3). Studies in cells confirmed the preferential release of cargo in IR-induced senescent cells compared to proliferating cells, depending on MMP-3 levels. More- over, treatment with NPs(Nav)@MMP-3 induced a selective decrease in the viability of SCs as well as a protective effect on non-proliferating cells. These results demonstrate the potential use of NPs to develop enhanced senolytic therapies based on specific enzymatic activity in the senescent microenvironment, with potential clinical relevance.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-03-01
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/10251/214710
url https://riunet.upv.es/handle/10251/214710
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 PID2021-128141OB-C22 DESARROLLO DE NUEVOS MATERIALES INTELIGENTES Y SU APLICACION COMO SISTEMAS ANTIVIRALES, ANTIBIOFILM, ANTIENZIMATICOS Y ANTIMICROBIANOS PARA LA INDUSTRIA ALIMENTARIA.
European Research Council https://doi.org/10.13039/501100000781 101052997
Generalitat Valenciana https://doi.org/10.13039/501100003359 CIPROM%2F2021%2F007
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 IFI19%2F00026
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CB06%2F01%2F2012 CIBER-BBN
Ministerio de Universidades MIU UP2021-036
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 A navitoclax-loaded nanodevice targeting matrix metalloproteinase-3 for the selective elimination of senescent cellsEscriche-Navarro, BlancaGarrido-García, Eva MaríaSancenón Galarza, Félix|||0000-0002-5205-7135García-Fernández, Alba|||0000-0002-8416-1674Martínez-Máñez, Ramón|||0000-0001-5873-9674Matrix metalloproteinase-3Mesoporous silica nanoparticlesSenescenceNavitoclaxQUIMICA ORGANICAQUIMICA INORGANICA[EN] Cellular senescence is implicated in the occurrence and progression of multiple age-related disorders. In this context, the selective elimination of senescent cells, senolysis, has emerged as an effective therapeu- tic strategy. However, the heterogeneous senescent phenotype hinders the discovery of a universal and robust senescence biomarker that limits the effective of senolytic with off-target toxic effects. Therefore, the development of more selective strategies represents a promising approach to increase the specificity of senolytic therapy. In this study, we have developed an innovative nanodevice for the selective elimi- nation of senescent cells (SCs) based on the specific enzymatic activity of the senescent secretome. The results revealed that when senescence is induced in proliferating WI-38 by ionizing radiation (IR), the cells secrete high levels of matrix metalloproteinase-3 (MMP-3). Based on this result, mesoporous silica nanoparticles (MSNs) were loaded with the senolytic navitoclax (Nav) and coated with a specific peptide which is substrate of MMP-3 (NPs(Nav)@MMP-3). Studies in cells confirmed the preferential release of cargo in IR-induced senescent cells compared to proliferating cells, depending on MMP-3 levels. More- over, treatment with NPs(Nav)@MMP-3 induced a selective decrease in the viability of SCs as well as a protective effect on non-proliferating cells. These results demonstrate the potential use of NPs to develop enhanced senolytic therapies based on specific enzymatic activity in the senescent microenvironment, with potential clinical relevance.This research was supported by projects PID2021-126304OBC41 and PID2021-128141OB-C22 funded by MCIN/ AEI /10.13039/501100011033/ and by European Regional Development Fund - A way of doing Europe. This study was also supported by Generalitat Valenciana (CIPROM/2021/007). This research was supported by CIBER (CB06/01/2012), Instituto de Salud Carlos III and Ministerio de Ciencia e Innovación. This work was also supported by the European Research Council (ERC) via Advanced Grant (101052997, EDISON). B.E-N. is grateful to the Instituto de Salud Carlos III (ISCIII) for the grant through the project IFI19/00026 , co-funded by the European Union and the company Senolytic Therapeutics S.L for the support. E.G. is grateful to the Spanish MIU and European Union-Next Regeneration EU for her Margarita Salas postdoctoral grant (UP2021-036).ElsevierDepartamento de QuímicaEscuela Técnica Superior de Ingeniería IndustrialInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo TecnológicoGeneralitat ValencianaEuropean Research CouncilMinisterio de UniversidadesInstituto de Salud Carlos IIIAgencia Estatal de InvestigaciónUniversitat Politècnica de ValènciaRepositorio Institucional de la Universitat Politècnica de València Riunet20242024-03-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/214710reponame: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 PID2021-128141OB-C22 DESARROLLO DE NUEVOS MATERIALES INTELIGENTES Y SU APLICACION COMO SISTEMAS ANTIVIRALES, ANTIBIOFILM, ANTIENZIMATICOS Y ANTIMICROBIANOS PARA LA INDUSTRIA ALIMENTARIA.European Research Council https://doi.org/10.13039/501100000781 101052997Generalitat Valenciana https://doi.org/10.13039/501100003359 CIPROM%2F2021%2F007Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 IFI19%2F00026Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 CB06%2F01%2F2012 CIBER-BBNMinisterio de Universidades MIU UP2021-036open 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:10251/2147102026-06-13T07:49:27Z
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