Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars

[EN] Bioorthogonal chemistry that can be controlled through near-infrared (NIR) light is a promising route to therapeutics. This study proposes a method to intracellularly photoactivate prodrugs using plasmonic gold nanostars (AuNSt) and NIR irradiation. Two strategies are followed. On one hand, dox...

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Autores: Esteve-Moreno, Juan José|||0000-0002-1259-7663, Escudero-Noguera, Andrea|||0000-0003-2670-6127, Terrés-Haro, José Manuel|||0000-0001-5794-7332, Sancenón Galarza, Félix|||0000-0002-5205-7135, García-Fernández, Alba|||0000-0002-8416-1674, Hernández-Montoto, Andy|||0000-0001-5623-9836, Martínez-Máñez, Ramón|||0000-0001-5873-9674, Ferreira Silvestre, Óscar, Gorbe, Mónica, Garrido, Eva, Renero-Lecuna, Carlos, Langer, Judith, Alfonso, María, Ibañez, J., Roberto Cao Milán, Liz-Marzán, Luis M.
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universitat Politècnica de València (UPV)
Repositorio:RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
Idioma:inglés
OAI Identifier:oai:riunet.upv.es:10251/229929
Acesso em linha:https://riunet.upv.es/handle/10251/229929
Access Level:acceso abierto
Palavra-chave:Bioorthogonal chemistry
Cancer therapy
Doxorubicin
Gold nanostars
Near infrared radiation
Photocleavable linkers
Prodrugs photoactivation
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oai_identifier_str oai:riunet.upv.es:10251/229929
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
title Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
spellingShingle Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
Esteve-Moreno, Juan José|||0000-0002-1259-7663
Bioorthogonal chemistry
Cancer therapy
Doxorubicin
Gold nanostars
Near infrared radiation
Photocleavable linkers
Prodrugs photoactivation
title_short Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
title_full Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
title_fullStr Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
title_full_unstemmed Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
title_sort Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold Nanostars
dc.creator.none.fl_str_mv Esteve-Moreno, Juan José|||0000-0002-1259-7663
Escudero-Noguera, Andrea|||0000-0003-2670-6127
Terrés-Haro, José Manuel|||0000-0001-5794-7332
Sancenón Galarza, Félix|||0000-0002-5205-7135
García-Fernández, Alba|||0000-0002-8416-1674
Hernández-Montoto, Andy|||0000-0001-5623-9836
Martínez-Máñez, Ramón|||0000-0001-5873-9674
Ferreira Silvestre, Óscar
Gorbe, Mónica
Garrido, Eva
Renero-Lecuna, Carlos
Langer, Judith
Alfonso, María
Ibañez, J.
Roberto Cao Milán
Liz-Marzán, Luis M.
author Esteve-Moreno, Juan José|||0000-0002-1259-7663
author_facet Esteve-Moreno, Juan José|||0000-0002-1259-7663
Escudero-Noguera, Andrea|||0000-0003-2670-6127
Terrés-Haro, José Manuel|||0000-0001-5794-7332
Sancenón Galarza, Félix|||0000-0002-5205-7135
García-Fernández, Alba|||0000-0002-8416-1674
Hernández-Montoto, Andy|||0000-0001-5623-9836
Martínez-Máñez, Ramón|||0000-0001-5873-9674
Ferreira Silvestre, Óscar
Gorbe, Mónica
Garrido, Eva
Renero-Lecuna, Carlos
Langer, Judith
Alfonso, María
Ibañez, J.
Roberto Cao Milán
Liz-Marzán, Luis M.
author_role author
author2 Escudero-Noguera, Andrea|||0000-0003-2670-6127
Terrés-Haro, José Manuel|||0000-0001-5794-7332
Sancenón Galarza, Félix|||0000-0002-5205-7135
García-Fernández, Alba|||0000-0002-8416-1674
Hernández-Montoto, Andy|||0000-0001-5623-9836
Martínez-Máñez, Ramón|||0000-0001-5873-9674
Ferreira Silvestre, Óscar
Gorbe, Mónica
Garrido, Eva
Renero-Lecuna, Carlos
Langer, Judith
Alfonso, María
Ibañez, J.
Roberto Cao Milán
Liz-Marzán, Luis M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Ingeniería Electrónica
Escuela Técnica Superior de Ingeniería de Telecomunicación
Escuela Técnica Superior de Ingeniería Aeroespacial y Diseño Industrial
Departamento de Química
Instituto Universitario de Automática e Informática Industrial
Escuela Técnica Superior de Ingeniería Industrial
Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico
European Commission
Generalitat Valenciana
Agencia Estatal de Investigación
Asociación Española Contra el Cáncer
Centro de Investigación Biomédica en Red
Universitat Politècnica de València
Repositorio Institucional de la Universitat Politècnica de València Riunet
dc.subject.none.fl_str_mv Bioorthogonal chemistry
Cancer therapy
Doxorubicin
Gold nanostars
Near infrared radiation
Photocleavable linkers
Prodrugs photoactivation
topic Bioorthogonal chemistry
Cancer therapy
Doxorubicin
Gold nanostars
Near infrared radiation
Photocleavable linkers
Prodrugs photoactivation
description [EN] Bioorthogonal chemistry that can be controlled through near-infrared (NIR) light is a promising route to therapeutics. This study proposes a method to intracellularly photoactivate prodrugs using plasmonic gold nanostars (AuNSt) and NIR irradiation. Two strategies are followed. On one hand, doxorubicin (Dox) masked with a 2-nitrobenzyl carbamate (proDox1) is used as a photoactivatable prodrug. In the second strategy, a photolabile Dox prodrug (proDox2) obtained by modification of Dox with 2-nitrobenzyl diol bearing a disulfide is attached to the AuNSt surface. Under NIR irradiation AuNSt induce local electromagnetic field enhancement, leading to photocleavage of the 2-nitrobenzyl moiety in both proDox1 and proDox2, and subsequent Dox release. Near field enhancement by excitation of surface plasmons in AuNSt is sufficient to record the surface-enhanced Raman scattering (SERS) spectra of proDox1 and proDox2. The therapeutic potential of this bioorthogonal photoactivation strategy is confirmed in vitro and in vivo using a mouse model of human melanoma. NIR-activated AuNSt induce in vivo the intracellular release of Dox and subsequent cancer cell death, thus reducing tumor growth at low irradiation power density to avoid undesired photothermal effects. These results demonstrate that AuNSt are suitable platforms for NIR light-triggered drug delivery in cancer therapy.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-09-01
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/10251/229929
url https://riunet.upv.es/handle/10251/229929
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 Commission https://doi.org/10.13039/501100000780 HE 101052997 Engineered Particles for Chemical Communication
Generalitat Valenciana https://doi.org/10.13039/501100003359 CIPROM%2F2021%2F007
Asociación Española Contra el Cáncer AECC PRDVA21651ESTE
Centro de Investigación Biomédica en Red CIBER CB06%2F01%2F2012
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 John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
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
_version_ 1869420434070437888
spelling Bioorthogonal Photoactivation of 2-Nitrobenzyl Caged Doxorubicin Anticancer Prodrugs on Gold NanostarsEsteve-Moreno, Juan José|||0000-0002-1259-7663Escudero-Noguera, Andrea|||0000-0003-2670-6127Terrés-Haro, José Manuel|||0000-0001-5794-7332Sancenón Galarza, Félix|||0000-0002-5205-7135García-Fernández, Alba|||0000-0002-8416-1674Hernández-Montoto, Andy|||0000-0001-5623-9836Martínez-Máñez, Ramón|||0000-0001-5873-9674Ferreira Silvestre, ÓscarGorbe, MónicaGarrido, EvaRenero-Lecuna, CarlosLanger, JudithAlfonso, MaríaIbañez, J.Roberto Cao MilánLiz-Marzán, Luis M.Bioorthogonal chemistryCancer therapyDoxorubicinGold nanostarsNear infrared radiationPhotocleavable linkersProdrugs photoactivation[EN] Bioorthogonal chemistry that can be controlled through near-infrared (NIR) light is a promising route to therapeutics. This study proposes a method to intracellularly photoactivate prodrugs using plasmonic gold nanostars (AuNSt) and NIR irradiation. Two strategies are followed. On one hand, doxorubicin (Dox) masked with a 2-nitrobenzyl carbamate (proDox1) is used as a photoactivatable prodrug. In the second strategy, a photolabile Dox prodrug (proDox2) obtained by modification of Dox with 2-nitrobenzyl diol bearing a disulfide is attached to the AuNSt surface. Under NIR irradiation AuNSt induce local electromagnetic field enhancement, leading to photocleavage of the 2-nitrobenzyl moiety in both proDox1 and proDox2, and subsequent Dox release. Near field enhancement by excitation of surface plasmons in AuNSt is sufficient to record the surface-enhanced Raman scattering (SERS) spectra of proDox1 and proDox2. The therapeutic potential of this bioorthogonal photoactivation strategy is confirmed in vitro and in vivo using a mouse model of human melanoma. NIR-activated AuNSt induce in vivo the intracellular release of Dox and subsequent cancer cell death, thus reducing tumor growth at low irradiation power density to avoid undesired photothermal effects. These results demonstrate that AuNSt are suitable platforms for NIR light-triggered drug delivery in cancer therapy.This research was supported by project PID2021-126304OB-C41 and PID2021-128141OB-C22 funded by MCIN/AEI/10.13039/501100011033/and by European Regional Development Fund-A way of doing Europe. The work was also supported by Generalitat Valenciana (CIPROM/2021/007). This study was also supported by the ERC Advanced Grant Edison (101052997). This research was supported by CIBER-Consorcio Centro de Investigacion Biomedica en Red-(CB06/01/2012), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion. J. J. E-M. thanks the financial support from FC AECC and especially to the AECC Council of Valencia for the trust placed (PRDVA21651ESTE). O.F.S. acknowledges the support from the Provincial Council of Gipuzkoa under the program Fellows Gipuzkoa. The authors thank the UPV electron microscopy and CIPF confocal and electron microscopy services for technical support.John Wiley & SonsDepartamento de Ingeniería ElectrónicaEscuela Técnica Superior de Ingeniería de TelecomunicaciónEscuela Técnica Superior de Ingeniería Aeroespacial y Diseño IndustrialDepartamento de QuímicaInstituto Universitario de Automática e Informática IndustrialEscuela Técnica Superior de Ingeniería IndustrialInstituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo TecnológicoEuropean CommissionGeneralitat ValencianaAgencia Estatal de InvestigaciónAsociación Española Contra el CáncerCentro de Investigación Biomédica en RedUniversitat Politècnica de ValènciaRepositorio Institucional de la Universitat Politècnica de València Riunet20252025-09-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://riunet.upv.es/handle/10251/229929reponame: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 Commission https://doi.org/10.13039/501100000780 HE 101052997 Engineered Particles for Chemical CommunicationGeneralitat Valenciana https://doi.org/10.13039/501100003359 CIPROM%2F2021%2F007Asociación Española Contra el Cáncer AECC PRDVA21651ESTECentro de Investigación Biomédica en Red CIBER CB06%2F01%2F2012open 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:10251/2299292026-06-13T07:49:27Z
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