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Horseradish Peroxidase-Functionalized Gold Nanoconjugates for Breast Cancer Treatment Based on Enzyme Prodrug Therapy

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Horseradish Peroxidase-Functionalized Gold Nanoconjugates for Breast Cancer Treatment Based on Enzyme Prodrug Therapy

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dc.contributor.author Vivo-Llorca, Gema es_ES
dc.contributor.author Morella-Aucejo, Ángela es_ES
dc.contributor.author García-Fernández, Alba es_ES
dc.contributor.author Diez-Sánchez, Paula es_ES
dc.contributor.author Llopis-Lorente, Antoni es_ES
dc.contributor.author Orzáez, Mar es_ES
dc.contributor.author Martínez-Máñez, Ramón es_ES
dc.date.accessioned 2023-03-28T18:00:48Z
dc.date.available 2023-03-28T18:00:48Z
dc.date.issued 2022-01-26 es_ES
dc.identifier.issn 1176-9114 es_ES
dc.identifier.uri http://hdl.handle.net/10251/192642
dc.description.abstract [EN] Introduction: Breast cancer has the highest mortality rate among cancers in women. Patients suffering from certain breast cancers, such as triple-negative breast cancer (TNBC), lack effective treatments. This represents a clinical concern due to the associated poor prognosis and high mortality. As an approach to succeed over conventional therapy limitations, we present herein the design and evaluation of a novel nanodevice based on enzyme-functionalized gold nanoparticles to efficiently perform enzyme prodrug therapy (EPT) in breast cancer cells. Results: In particular, the enzyme horseradish peroxidase (HRP) which oxidizes the prodrug indole-3-acetic acid (IAA) to release toxic oxidative species is incorporated on gold nanoconjugates (HRP-AuNCs), obtaining an efficient nanoplatform for EPT. The nanodevice is biocompatible and effectively internalized by breast cancer cell lines. Remarkably, co-treatment with HRP-AuNCs and IAA (HRP-AuNCs/IAA) reduces the viability of breast cancer cells below 5%. Interestingly, 3D tumor models (multicellular tumor spheroid-like cultures) co-treated with HRP-AuNCs/IAA exhibit a 74% reduction of cell viability, whereas the free formulated components (HRP, IAA) have no effect. Conclusion: Altogether, our results demonstrate that the designed HRP-AuNCs nanoformulation shows a remarkable therapeutic performance. These findings might help to bypass the clinical limitations of current tumor enzyme therapies and advance towards the use of nanoformulations for EPT in breast cancer. es_ES
dc.description.sponsorship Gema Vivo-Llorca thanks the Generalitat Valenciana for her fellowship ACIF/2017/072. Paula Díez thanks the Generalitat Valenciana for her contract APOSTD/2020/153 and to the Instituto de Salud Carlos III and the European Social Fund for the financial support "Sara Borrell", CD20/00120. Antoni Llopis-Lorente thanks funding from the European Union¿s Horizon 2020 research and innovation programme under grant agreement No 847675. Images were prepared using Servier Medical Art (https://smart.servier.com/). We thank the Spanish Government (project RTI2018-100910-B-C41 (MCUI/AEI/FEDER, UE); SAF2017-84689-R-B (MCUI/ AEI/FEDER, UE)) and the Generalitat Valenciana (project PROMETEO/2018/024 and PROMETEO/2019/065) for support. A pre-print version of this work was published as a chapter of the PhD thesis of the first author Gema VivoLlorca es_ES
dc.language Inglés es_ES
dc.publisher Dove Medical Press es_ES
dc.relation.ispartof International Journal of Nanomedicine es_ES
dc.rights Reconocimiento - No comercial (by-nc) es_ES
dc.subject Gold nanoconjugates es_ES
dc.subject Horseradish peroxidase es_ES
dc.subject Indole-3-acetic acid es_ES
dc.subject Enzyme prodrug therapy es_ES
dc.subject Breast cancer es_ES
dc.subject.classification QUIMICA INORGANICA es_ES
dc.title Horseradish Peroxidase-Functionalized Gold Nanoconjugates for Breast Cancer Treatment Based on Enzyme Prodrug Therapy es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.2147/IJN.S323802 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-100910-B-C41/ES/MATERIALES POROSOS INTELIGENTES MULTIFUNCIONALES Y DISPOSITIVOS ELECTRONICOS PARA LA LIBERACION DE FARMACOS, DETECCION DE DROGAS Y BIOMARCADORES Y COMUNICACION A NANOESCALA/
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847675/EU
dc.relation.projectID info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-84689-R/ES/DESCIFRANDO Y MODULANDO EL INTERACTOMA TRANSMEMBRANA DE LAS PROTEINAS BCL-2 COMO DIANA ANTITUMORAL/
dc.relation.projectID info:eu-repo/grantAgreement/GVA//ACIF/2017/072/ES/AYUDA PREDOCTORAL CONSELLERIA-VIVO LLORCA
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Escuela Técnica Superior de Ingenieros Industriales - Escola Tècnica Superior d'Enginyers Industrials es_ES
dc.description.bibliographicCitation Vivo-Llorca, G.; Morella-Aucejo, Á.; García-Fernández, A.; Diez-Sánchez, P.; Llopis-Lorente, A.; Orzáez, M.; Martínez-Máñez, R. (2022). Horseradish Peroxidase-Functionalized Gold Nanoconjugates for Breast Cancer Treatment Based on Enzyme Prodrug Therapy. International Journal of Nanomedicine. 17:409-422. https://doi.org/10.2147/IJN.S323802 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.2147/IJN.S323802 es_ES
dc.description.upvformatpinicio 409 es_ES
dc.description.upvformatpfin 422 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 17 es_ES
dc.identifier.pmid 35115775 es_ES
dc.identifier.pmcid PMC8802903 es_ES
dc.relation.pasarela S\456016 es_ES
dc.contributor.funder Agencia Estatal de Investigación
dc.contributor.funder European Commission
dc.contributor.funder Generalitat Valenciana
upv.costeAPC 3023 es_ES


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