000118282 001__ 118282 000118282 005__ 20240319081018.0 000118282 0247_ $$2doi$$a10.1039/d2sc01379g 000118282 0248_ $$2sideral$$a129477 000118282 037__ $$aART-2022-129477 000118282 041__ $$aeng 000118282 100__ $$0(orcid)0000-0002-1791-0188$$aBonet-Aletá, Javier$$uUniversidad de Zaragoza 000118282 245__ $$aUnveiling the interplay between homogeneous and heterogeneous catalytic mechanisms in copper-iron nanoparticles working under chemically relevant tumour conditions 000118282 260__ $$c2022 000118282 5060_ $$aAccess copy available to the general public$$fUnrestricted 000118282 5203_ $$aThe present work sheds light on a generally overlooked issue in the emerging field of bio-orthogonal catalysis within tumour microenvironments (TMEs): the interplay between homogeneous and heterogeneous catalytic processes. In most cases, previous works dealing with nanoparticle-based catalysis in the TME focus on the effects obtained (e.g. tumour cell death) and attribute the results to heterogeneous processes alone. The specific mechanisms are rarely substantiated and, furthermore, the possibility of a significant contribution of homogeneous processes by leached species - and the complexes that they may form with biomolecules - is neither contemplated nor pursued. Herein, we have designed a bimetallic catalyst nanoparticle containing Cu and Fe species and we have been able to describe the whole picture in a more complex scenario where both homogeneous and heterogeneous processes are coupled and fostered under TME relevant chemical conditions. We investigate the preferential leaching of Cu ions in the presence of a TME overexpressed biomolecule such as glutathione (GSH). We demonstrate that these homogeneous processes initiated by the released by Cu-GSH interactions are in fact responsible for the greater part of the cell death effects found (GSH, a scavenger of reactive oxygen species, is depleted and highly active superoxide anions are generated in the same catalytic cycle). The remaining solid CuFe nanoparticle becomes an active catalyst to supply oxygen from oxygen reduced species, such as superoxide anions (by-product from GSH oxidation) and hydrogen peroxide, another species that is enriched in the TME. This activity is essential to sustain the homogeneous catalytic cycle in the oxygen-deprived tumour microenvironment. The combined heterogeneous-homogeneous mechanisms revealed themselves as highly efficient in selectively killing cancer cells, due to their higher GSH levels compared to healthy cell lines. 000118282 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E19-20R$$9info:eu-repo/grantAgreement/EC/H2020/742684/EU/Catalytic Dual-Function Devices Against Cancer/CADENCE$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 742684-CADENCE 000118282 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/ 000118282 590__ $$a8.4$$b2022 000118282 592__ $$a2.762$$b2022 000118282 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b32 / 178 = 0.18$$c2022$$dQ1$$eT1 000118282 593__ $$aChemistry (miscellaneous)$$c2022$$dQ1 000118282 594__ $$a15.2$$b2022 000118282 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000118282 700__ $$aEncinas-Giménez, Miguel$$uUniversidad de Zaragoza 000118282 700__ $$0(orcid)0000-0001-9779-5820$$aUrriolabeitia, Esteban 000118282 700__ $$0(orcid)0000-0003-4160-9720$$aMartín-Duque, Pilar$$uUniversidad de Zaragoza 000118282 700__ $$0(orcid)0000-0002-4546-4111$$aHueso, José L.$$uUniversidad de Zaragoza 000118282 700__ $$0(orcid)0000-0002-8701-9745$$aSantamaría, Jesús$$uUniversidad de Zaragoza 000118282 7102_ $$11013$$2275$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Estomatología 000118282 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química 000118282 773__ $$g13, 28 (2022), 8307-8320$$pChem. sci.$$tCHEMICAL SCIENCE$$x2041-6520 000118282 8564_ $$s2240504$$uhttps://zaguan.unizar.es/record/118282/files/texto_completo.pdf$$yVersión publicada 000118282 8564_ $$s2689402$$uhttps://zaguan.unizar.es/record/118282/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000118282 909CO $$ooai:zaguan.unizar.es:118282$$particulos$$pdriver 000118282 951__ $$a2024-03-18-15:55:54 000118282 980__ $$aARTICLE