000149051 001__ 149051
000149051 005__ 20250124153131.0
000149051 0247_ $$2doi$$a10.1021/acsbiomaterials.4c00771
000149051 0248_ $$2sideral$$a142163
000149051 037__ $$aART-2024-142163
000149051 041__ $$aeng
000149051 100__ $$aWnuk, Maciej
000149051 245__ $$aDesign of a Magnetic Nanoplatform Based on CD26 Targeting and HSP90 Inhibition for Apoptosis and Ferroptosis-Mediated Elimination of Senescent Cells
000149051 260__ $$c2024
000149051 5060_ $$aAccess copy available to the general public$$fUnrestricted
000149051 5203_ $$aThe 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.
000149051 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E15-23R$$9info:eu-repo/grantAgreement/EC/HORIZON EUROPE/101064735/EU/Tunning the force for remote magnetomechanical gating of Piezo1 channels/MAGPIEZ$$9info:eu-repo/grantAgreement/EC/H2020/853468/EU/Remote control of cellular signalling triggered by magnetic switching/SIROCCO$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 853468-SIROCCO$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-122508NB-I00$$9info:eu-repo/grantAgreement/ES/MICIU/PCI2023-143448
000149051 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000149051 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000149051 700__ $$aDel Sol-Fernández, Susel
000149051 700__ $$aBloniarz, Dominika
000149051 700__ $$aSlaby, Julia
000149051 700__ $$aSzmatola, Tomasz
000149051 700__ $$aZebrowski, Michal
000149051 700__ $$aMartínez-Vicente, Pablo$$uUniversidad de Zaragoza
000149051 700__ $$aLitwinienko, Grzegorz
000149051 700__ $$aMoros, María
000149051 700__ $$aLewinska, Anna
000149051 7102_ $$11002$$2807$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Toxicología
000149051 773__ $$g11, 1 (2024), 280-297$$pACS biomater. sci. eng.$$tACS BIOMATERIALS SCIENCE & ENGINEERING$$x2373-9878
000149051 8564_ $$s10908371$$uhttps://zaguan.unizar.es/record/149051/files/texto_completo.pdf$$yVersión publicada
000149051 8564_ $$s3284612$$uhttps://zaguan.unizar.es/record/149051/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000149051 909CO $$ooai:zaguan.unizar.es:149051$$particulos$$pdriver
000149051 951__ $$a2025-01-24-14:49:42
000149051 980__ $$aARTICLE