RT Journal Article
T1 Silver clusters of five atoms as highly selective antitumoral agents through irreversible oxidation of thiols
A1 Porto González, Vanesa
A1 Buceta Fernández, David
A1 Domínguez Loidi, Blanca
A1 Carneiro Freire, María del Carmen
A1 Borrajo Alonso, Erea
A1 Fraile Piñeiro, María
A1 Davila Ferreira, Nerea
A1 Rodríguez Arias, Iria
A1 Blanco Trillo, José Manuel
A1 Blanco Varela, María del Carmen
A1 Devida, Juan Marcelo
A1 Giovanetti, Lisandro José
A1 Requejo, Félix Gregorio
A1 Hernández Garrido, Juan Carlos
A1 Calvino Gámez, José Juan
A1 López Haro, Miguel
A1 Barone, Giampaolo
A1 James, Andrew M.
A1 García-Caballero Parada, Tomás
A1 González Castaño, Diego Miguel
A1 Treder, Martin
A1 Huber, Wolfgang
A1 Vidal Figueroa, Anxo
A1 Michael, P. Murphy
A1 López Quintela, Manuel Arturo
A1 Domínguez Puente, Fernando Ignacio
K1 Cancer therapy
K1 Catalysis
K1 Low atomicity clusters
K1 Silver clusters
K1 Sulfur oxidation
AB 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
PB Wiley
SN 1616-301X
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29229
UL http://hdl.handle.net/10347/29229
LA eng
NO 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
NO 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)
DS Minerva
RD 24 abr 2026