162911 20251009133840.0 doi 10.1039/d5nr01927c sideral 145400 ART-2025-145400 eng Encinas-Gimenez, Miguel Unravelling the cell death mechanism triggered by catalytic copper–iron nanoparticles <i>in vitro</i> and <i>in vivo</i> 2025 Access copy available to the general public Unrestricted Nanomedicine has developed an impressive array of anticancer devices, from drug delivery vectors to hyperthermia-enabling nanoparticles. Lately, emphasis has been shifted to the tumour microenvironment (TME) and to active nanomaterials adapted to the prevailing conditions. Among them, catalytic nanomaterials (also called nanocatalysts) represent a highly interesting alternative, especially when they are able to target metabolites that are present to a greater extent in tumoral cells, opening a window for a catalytically selective action. In this context, herein, we present an in-depth study of the working mechanisms of a meso-2,3-dimercaptosuccinic acid-coated, copper- and iron-based nanoparticle (CuFe@DMSA NPs) with high capability of glutathione (GSH) depletion with simultaneous production of reactive oxygen species (ROS). GSH is an important molecule with antioxidant properties, which is overexpressed in a broad range of tumoral cells, and these CuFe@DMSA NPs catalyse its conversion by means of leached copper ions. In this work, the metabolic action of this nanomaterial on tumoral cells has been thoroughly described, demonstrating that cells underwent a ferroptosis-like cell death, together with the arrest of the cell cycle and induction of apoptosis. The obtained in vitro results were further confirmed in vivo, showing that the increase of apoptosis leads to a significant reduction of tumour growth in treated mice. info:eu-repo/grantAgreement/EUR/ERC/ERC-AdG-742684 info:eu-repo/grantAgreement/ES/MICIU/CEX2023-001286-S info:eu-repo/semantics/embargoedAccess All rights reserved http://www.europeana.eu/rights/rr-f/ info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Martín-Pardillos, Ana Universidad de Zaragoza Bonet-Aleta, Javier (orcid)0000-0002-1791-0188 Pérez, Estela Rodríguez-Largo, Ana (orcid)0000-0002-2685-1730 Hueso, Jose L. Universidad de Zaragoza (orcid)0000-0002-4546-4111 Santamaria, Jesus Universidad de Zaragoza (orcid)0000-0002-8701-9745 Martin-Duque, Pilar Universidad de Zaragoza (orcid)0000-0003-4160-9720 1013 275 Universidad de Zaragoza Dpto. Cirugía Área Estomatología 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 5005 790 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Tecnologi. Medio Ambiente 1002 807 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Toxicología (2025), [17 pp.] Nanoscale Nanoscale 2040-3364 3923468 http://zaguan.unizar.es/record/162911/files/texto_completo.pdf Postprint info:eu-repo/date/embargoEnd/2026-08-13 2901199 http://zaguan.unizar.es/record/162911/files/texto_completo.jpg?subformat=icon icon Postprint info:eu-repo/date/embargoEnd/2026-08-13 oai:zaguan.unizar.es:162911 articulos driver 2025-10-09-13:25:53 ARTICLE