Resumen: Heterogeneous catalysis has emerged as a promising alternative for the development of new cancer therapies. In addition, regarding the tumor microenvironment as a reactor with very specific chemical features has provided a new perspective in the search for catalytic nanoarchitectures with specific action against chemical species playing a key role in tumor metabolism. One of these species is glutathione (GSH), whose depletion is the cornerstone of emerging strategies in oncology, since this metabolite plays a pivotal regulatory role as antioxidant agent, dampening the harmful effects of intracellular reactive oxidative species (ROS). Herein, we present copper-iron oxide spinel nanoparticles that exhibit a versatile and selective catalytic response to reduce GSH levels while generating ROS in a cascade reaction. We demonstrate a clear correlation between GSH depletion and apoptotic cell death in tumor cells in the presence of the copper-iron nanocatalyst. Furthermore, we also provide a novel analytical protocol, alternative to state-of-the-art commercial kits, to accurately monitoring the concentration of GSH intracellular levels in both tumor and healthy cells. We observe a selective action of the nanoparticles, with lower toxicity in healthy cell lines, whose intrinsic GSH levels are lower, and intense apoptosis in tumor cells accompanied by a fast reduction of GSH levels. Idioma: Inglés DOI: 10.1016/j.jcis.2022.03.036 Año: 2022 Publicado en: Journal of Colloid and Interface Science 617 (2022), 704-717 ISSN: 0021-9797 Factor impacto JCR: 9.9 (2022) Categ. JCR: CHEMISTRY, PHYSICAL rank: 29 / 161 = 0.18 (2022) - Q1 - T1 Factor impacto CITESCORE: 15.5 - Chemical Engineering (Q1) - Materials Science (Q1)