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dc.contributor.author | Porto González, Vanesa |
dc.contributor.author | Buceta Fernández, David |
dc.contributor.author | Domínguez Loidi, Blanca |
dc.contributor.author | Carneiro Freire, María del Carmen |
dc.contributor.author | Borrajo Alonso, Erea |
dc.contributor.author | Fraile Piñeiro, María |
dc.contributor.author | Davila Ferreira, Nerea |
dc.contributor.author | Rodríguez Arias, Iria |
dc.contributor.author | Blanco Trillo, José Manuel |
dc.contributor.author | Blanco Varela, María del Carmen |
dc.contributor.author | Devida, Juan Marcelo |
dc.contributor.author | Giovanetti, Lisandro José |
dc.contributor.author | Requejo, Félix Gregorio |
dc.contributor.author | Hernández Garrido, Juan Carlos |
dc.contributor.author | Calvino Gámez, José Juan |
dc.contributor.author | López Haro, Miguel |
dc.contributor.author | Barone, Giampaolo |
dc.contributor.author | James, Andrew M. |
dc.contributor.author | García-Caballero Parada, Tomás |
dc.contributor.author | González Castaño, Diego Miguel |
dc.contributor.author | Treder, Martin |
dc.contributor.author | Huber, Wolfgang |
dc.contributor.author | Vidal Figueroa, Anxo |
dc.contributor.author | Michael, P. Murphy |
dc.contributor.author | López Quintela, Manuel Arturo |
dc.contributor.author | Domínguez Puente, Fernando Ignacio |
dc.date.accessioned | 2022-09-19T11:19:51Z |
dc.date.available | 2022-09-19T11:19:51Z |
dc.date.issued | 2022 |
dc.identifier.citation | Porto, V., Buceta, D., Domínguez, B., Carneiro, C., Borrajo, E., Fraile, M., . . . Domínguez, F. (2022). Silver clusters of five atoms as highly selective antitumoral agents through irreversible oxidation of thiols. Advanced Functional Materials, 32(29), 2113028-n/a |
dc.identifier.issn | 1616-301X |
dc.identifier.uri | http://hdl.handle.net/10347/29229 |
dc.description.abstract | Low atomicity clusters present properties dependent on the size, due to the quantum confinement, with well-defined electronic structures and high stability. Here it is shown that Ag5 clusters catalyze the complete oxidation of sulfur to S+6. Ag5 catalytic activity increases with different oxidant species in the order O2 ≪ H2O2 < OH•. Selective oxidation of thiols on the cysteine residues of glutathione and thioredoxin is the primary mechanism human cells have to maintain redox homeostasis. Contingent upon oxidant concentration, Ag5 catalyzes the irreversible oxidation of glutathione and thioredoxin, triggering apoptosis. Modification of the intracellular environment to a more oxidized state to mimic conditions within cancer cells through the expression of an activated oncogene (HRASG12V) or through ARID1A mutation, sensitizes cells to Ag5 mediated apoptosis. While cancers evolve to evade treatments designed to target pathways or genetic mutations that drive them, they cannot evade a treatment that takes advantage of aberrant redox homeostasis, which is essential for tumor progression and metastasis. Ag5 has antitumor activity in mice with orthotopic lung tumors reducing primary tumor size, and the burden of affected lymphatic nodes. The findings suggest the unique intracellular redox chemistry of Ag5 may lead to new redox-based approaches to cancer therapy |
dc.description.sponsorship | This research was partially supported by 1) “la Caixa” Foundation, Ref. LCF/PR/PR12/11070003 to F.D. and M.A.L.Q.; 2) Ministerio de Ciencia, Innovación y Universidades (MAT2017-89678-R, AEI/FEDER, UE) to F.D. and A.V.; 3) the Consellería de Educación (Xunta de Galicia), Grants No. Grupos Ref. Comp. ED431C 2017/22, ED431C 2019/13 and AEMAT-ED431E2018/08 to M.A.L.Q.; and ED431C 2019/13 to A.V. This project has received funding from the European Union's Horizon 2020 Research and Innovation Programme (Bac-To-Fuel) under Grant Agreement No. 825999 (M.A.L.Q.). J.C.H. acknowledge financial support from European Union's Horizon 2020 research and innovation programme under grant agreement no. 823717-ESTEEM3, and the MICIIN (projects PID2019-107578GA-100 and PID-110018GA-100). J.M.D, L.J.G., and F.G.R. thank to the ANPCyT (PICT 2015-2285 and 2017-3944), UNLP (Project 11/X790) and the partial support by the Laboratório Nacional de Luz Síncrotron (LNLS, Brazil) under proposal SXS-20180280. G.B. acknowledges the CINECA Award N. IsC51, year 2017, under the ISCRA initiative, for the availability of high-performance computing resources and support. D.B. expresses gratitude for a postdoctoral grant from Xunta de Galicia, Spain (POS-A/2013/018). B.D. expresses gratitude for a predoctoral grant from MICINN, Spain (BES-2016-076765). F.D. and A.V. also acknowledged Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022 ref ED431G 2019/02) and the European Union (European Regional Development Fund – ERDF). Work in M.P.M.'s lab was supported by the Medical Research Council UK (MC_U105663142). T.G.C. gratefully acknowledges the technical assistance of María José Otero-Fraga (FIDIS) |
dc.language.iso | eng |
dc.publisher | Wiley |
dc.rights | © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited |
dc.rights | Atribución 4.0 Internacional |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.subject | Cancer therapy |
dc.subject | Catalysis |
dc.subject | Low atomicity clusters |
dc.subject | Silver clusters |
dc.subject | Sulfur oxidation |
dc.title | Silver clusters of five atoms as highly selective antitumoral agents through irreversible oxidation of thiols |
dc.type | journal article |
dc.identifier.doi | 10.1002/adfm.202113028 |
dc.relation.publisherversion | https://doi.org/10.1002/adfm.202113028 |
dc.type.hasVersion | VoR |
dc.identifier.essn | 1616-3028 |
dc.rights.accessRights | open access |
dc.contributor.affiliation | Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas |
dc.contributor.affiliation | Universidade de Santiago de Compostela. Departamento de Fisioloxía |
dc.contributor.affiliation | Universidade de Santiago de Compostela. Departamento de Química Física |
dc.description.peerreviewed | SI |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/825999 |
dc.relation.projectID | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/ PID2019-107578GA-I00/ES/COMBINACION DE PLASMONICA Y CATALISIS PARA EL DESARROLLO DE NANOESTRUCTURAS BASADAS EN MOS2 PARA APLICACIONES DE ENERGIA LIMPIA |
dc.relation.projectID | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/MAT2017-89678-R/ES/CLUSTERS ATOMICOS CUANTICOS DE PLATA: MECANISMOS DE ACCION BIOLOGICA Y APLICACIONES TERAPEUTICAS |
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© 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
© 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited