Glutathione-Triggered catalytic response of Copper-Iron mixed oxide Nanoparticles. Leveraging tumor microenvironment conditions for chemodynamic therapy
| Autor: | Javier Bonet-Aleta, Maria Sancho-Albero, Javier Calzada-Funes, Silvia Irusta, Pilar Martin-Duque, Jose L. Hueso, Jesus Santamaria |
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| Přispěvatelé: | European Research Council, European Commission, Instituto de Investigación Sanitaria Aragón, Instituto de Salud Carlos III |
| Rok vydání: | 2022 |
| Předmět: |
Cancer therapy
Iron Reactive oxidative species Fenton reactions Oxides Hydrogen Peroxide Nanocatalysis Glutathione Catalysis Surfaces Coatings and Films Electronic Optical and Magnetic Materials Biomaterials Colloid and Surface Chemistry Cell Line Tumor Neoplasms Tumor Microenvironment Cascade reactions Humans Nanoparticles Reactive Oxygen Species Copper |
| Zdroj: | Zaguán. Repositorio Digital de la Universidad de Zaragoza Consejo Superior de Investigaciones Científicas (CSIC) Digital.CSIC. Repositorio Institucional del CSIC instname Journal of Colloid and Interface Science |
| Popis: | 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. Financial support from the European Research Council (ERC-Advanced Grant CADENCE number 742684) is gratefully acknowledged. The TEM measurements were conducted at the Laboratorio de Microscopias Avanzadas, Instituto de Nanociencia de Aragon, Universidad de Zaragoza, Spain. The synthesis of materials has been performed by the Platform of Production of Biomaterials and Nanoparticles of the NANBIOSIS ICTS, more specifically by the Nanoparticle Synthesis Unit of the CIBER in BioEngineering, Biomaterials & Nanomedicine (CIBER-BBN). J.B-A. acknowledges the Spanish Government for an FPU predoctoral contract. We would also like to thank to the Scientific Services of the Aragon Institute of Health Sciences (IACS), specifically to the Cell culture, Microscopy, and Citometry Services and their specialist and the ICTS ELECMI. |
| Databáze: | OpenAIRE |
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