149051 20260217205518.0 doi 10.1021/acsbiomaterials.4c00771 sideral 142163 ART-2024-142163 eng Wnuk, Maciej Design of a Magnetic Nanoplatform Based on CD26 Targeting and HSP90 Inhibition for Apoptosis and Ferroptosis-Mediated Elimination of Senescent Cells 2024 Access copy available to the general public Unrestricted The accumulation of senescent cells, a hallmark of aging and age-related diseases, is also considered as a side effect of anticancer therapies, promoting drug resistance and leading to treatment failure. The use of senolytics, selective inducers of cell death in senescent cells, is a promising pharmacological antiaging and anticancer approach. However, more studies are needed to overcome the limitations of first-generation senolytics by the design of targeted senolytics and nanosenolytics and the validation of their usefulness in biological systems. In the present study, we have designed a nanoplatform composed of iron oxide nanoparticles functionalized with an antibody against a cell surface marker of senescent cells (CD26), and loaded with the senolytic drug HSP90 inhibitor 17-DMAG (MNP@CD26@17D). We have documented its action against oxidative stress-induced senescent human fibroblasts, WI-38 and BJ cells, and anticancer drug-induced senescent cutaneous squamous cell carcinoma A431 cells, demonstrating for the first time that CD26 is a valid marker of senescence in cancer cells. A dual response to MNP@CD26@17D stimulation in senescent cells was revealed, namely, apoptosis-based early response (2 h treatment) and ferroptosis-based late response (24 h treatment). MNP@CD26@17D-mediated ferroptosis might be executed by ferritinophagy as judged by elevated levels of the ferritinophagy marker NCOA4 and a decreased pool of ferritin. As 24 h treatment with MNP@CD26@17D did not induce hemolysis in human erythrocytes in vitro, this newly designed nanoplatform could be considered as an optimal multifunctional tool to target and eliminate senescent cells of skin origin, overcoming their apoptosis resistance. info:eu-repo/grantAgreement/ES/DGA/E15-23R info:eu-repo/grantAgreement/EC/HORIZON EUROPE/101064735/EU/Tunning the force for remote magnetomechanical gating of Piezo1 channels/MAGPIEZ info:eu-repo/grantAgreement/EC/H2020/853468/EU/Remote control of cellular signalling triggered by magnetic switching/SIROCCO This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 853468-SIROCCO info:eu-repo/grantAgreement/ES/MICINN/PID2021-122508NB-I00 info:eu-repo/grantAgreement/ES/MICIU/PCI2023-143448 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 5.5 2024 MATERIALS SCIENCE, BIOMATERIALS 20 / 55 = 0.364 2024 Q2 T2 1.105 2024 Biomedical Engineering 2024 Q1 Biomaterials 2024 Q2 9.7 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Del Sol-Fernández, Susel Bloniarz, Dominika Slaby, Julia Szmatola, Tomasz Zebrowski, Michal Martínez-Vicente, Pablo Universidad de Zaragoza Litwinienko, Grzegorz Moros, María Lewinska, Anna 1002 807 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Toxicología 11, 1 (2024), 280-297 ACS biomater. sci. eng. ACS BIOMATERIALS SCIENCE & ENGINEERING 2373-9878 10908371 http://zaguan.unizar.es/record/149051/files/texto_completo.pdf Versión publicada 3284612 http://zaguan.unizar.es/record/149051/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:149051 articulos driver 2026-02-17-20:27:40 ARTICLE