000169156 001__ 169156 000169156 005__ 20260220162133.0 000169156 0247_ $$2doi$$a10.1039/d5sc09556e 000169156 0248_ $$2sideral$$a148239 000169156 037__ $$aART-2026-148239 000169156 041__ $$aeng 000169156 100__ $$0(orcid)0000-0002-1791-0188$$aBonet-Aleta, Javier 000169156 245__ $$aNanomedical approaches to deplete intracellular glutathione in oncology 000169156 260__ $$c2026 000169156 5060_ $$aAccess copy available to the general public$$fUnrestricted 000169156 5203_ $$aGlutathione (GSH) plays a critical role in maintaining redox homeostasis and conferring chemoresistance to cancer cells, making it an attractive target for therapeutic intervention. Recent advances in nanomedicine have led to the development of diverse nanostructures capable of depleting GSH, either stoichiometrically or catalytically. These systems exploit the elevated GSH demand in tumors to selectively disrupt redox balance, enhancing reactive oxygen species (ROS) accumulation and improving the efficacy of conventional therapies. Approaches include metal-based nanocatalysts, GSH-responsive prodrugs, and stimuli-activated platforms using light or ultrasound for spatiotemporal control. Despite promising preclinical outcomes, key challenges remain, including limited mechanistic understanding, variability in GSH sensitivity across cancer types, and a lack of standardized assays to evaluate GSH-depleting efficiency. Addressing these gaps will require cross-disciplinary efforts bridging materials science, chemical biology, and catalysis. Such integration is essential for translating GSH-targeting nanomedicines into effective clinical tools against drug-resistant malignancies. This perspective provides an overview of some of the most promising nanomaterials explored in the current state of the art and discusses the main strategies and challenges relevant to future clinical translation. 000169156 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2023-148732NB-I00$$9info:eu-repo/grantAgreement/ES/UZ-DGA/T57-23R$$9info:eu-repo/grantAgreement/ES/MICINN/CNS2022-135911$$9info:eu-repo/grantAgreement/ES/MICIU/CEX2023-001286-S 000169156 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es 000169156 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000169156 700__ $$0(orcid)0000-0002-4546-4111$$aHueso, Jose L.$$uUniversidad de Zaragoza 000169156 700__ $$aMosseri, Andrea 000169156 700__ $$0(orcid)0000-0002-8701-9745$$aSantamaria, Jesus$$uUniversidad de Zaragoza 000169156 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química 000169156 7102_ $$15005$$2790$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Tecnologi. Medio Ambiente 000169156 773__ $$g17, 4 (2026), 1911-1931$$pChem. sci.$$tCHEMICAL SCIENCE$$x2041-6520 000169156 8564_ $$s4781183$$uhttps://zaguan.unizar.es/record/169156/files/texto_completo.pdf$$yVersión publicada 000169156 8564_ $$s2794488$$uhttps://zaguan.unizar.es/record/169156/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000169156 909CO $$ooai:zaguan.unizar.es:169156$$particulos$$pdriver 000169156 951__ $$a2026-02-20-14:54:06 000169156 980__ $$aARTICLE