135753 20260217205540.0 doi 10.1021/acsami.4c04336 sideral 138649 ART-2024-138649 eng Bonet-Aleta, Javier Universidad de Zaragoza (orcid)0000-0002-1791-0188 Nanomedicine targeting cuproplasia in cancer: labile copper sequestration using polydopamine particles blocks tumor growth in vivo through altering metabolism and redox homeostasis 2024 Access copy available to the general public Unrestricted Copper plays critical roles as a metal active site cofactor and metallo-allosteric signal for enzymes involved in cell proliferation and metabolism, making it an attractive target for cancer therapy. In this study, we investigated the efficacy of polydopamine nanoparticles (PDA NPs), classically applied for metal removal from water, as a therapeutic strategy for depleting intracellular labile copper pools in triple negative breast cancer models through the metal-chelating groups present on PDA surface. By using the activity-based sensing probe FCP-1, we could track the PDA-induced labile copper depletion while leaving total copper levels unchanged, and link it to the selective MDA-MB-231 cell death. Further mechanistic investigations revealed that PDA NPs increased reactive oxygen species (ROS) levels, potentially through the inactivation of superoxide dismutase 1 (SOD1), a copper-dependent antioxidant enzyme. Additionally, PDA NPs were found to interact with the mitochondrial membrane, resulting in an increase in mitochondrial membrane potential, which may contribute to enhanced ROS production. We employed an in vivo tumor model to validate the therapeutic efficacy of PDA NPs. Remarkably, in the absence of any additional treatment, the presence of PDA NPs alone led to a significant reduction in tumor volume by a factor of 1.66 after 22 days of tumor growth. Our findings highlight the potential of PDA NPs as a promising therapeutic approach for selectively targeting cancer by modulating copper levels and inducing oxidative stress, leading to tumor growth inhibition as shown in these triple negative breast cancer models. info:eu-repo/grantAgreement/EC/H2020/742684/EU/Catalytic Dual-Function Devices Against Cancer/CADENCE This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 742684-CADENCE info:eu-repo/grantAgreement/ES/ISCIII DTS21-00130 info:eu-repo/grantAgreement/ES/ISCIII/PI19-01007 info:eu-repo/grantAgreement/ES/MICINN/PDC2022-133866-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2021-127847OB-I00 info:eu-repo/grantAgreement/ES/UZ/ICTS NANBIOSIS-CIBER-BBN info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 8.2 2024 NANOSCIENCE & NANOTECHNOLOGY 31 / 147 = 0.211 2024 Q1 T1 MATERIALS SCIENCE, MULTIDISCIPLINARY 83 / 461 = 0.18 2024 Q1 T1 1.921 2024 Materials Science (miscellaneous) 2024 Q1 Nanoscience and Nanotechnology 2024 Q1 Medicine (miscellaneous) 2024 Q1 14.5 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Encinas-Giménez, Miguel Universidad de Zaragoza Oi, Miku Pezacki, Aidan T. Sebastián, Víctor Universidad de Zaragoza (orcid)0000-0002-6873-5244 de Martino, Alba Martín-Pardillos, Ana Universidad de Zaragoza Martín-Duque, Pilar Universidad de Zaragoza (orcid)0000-0003-4160-9720 Hueso, José L. Universidad de Zaragoza (orcid)0000-0002-4546-4111 Chang, Christopher J. Santamaría, Jesús Universidad de Zaragoza (orcid)0000-0002-8701-9745 1013 275 Universidad de Zaragoza Dpto. Cirugía Área Estomatología 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 5005 790 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Tecnologi. Medio Ambiente 16, 23 (2024), 29844-29855 ACS appl. mater. interfaces ACS applied materials & interfaces 1944-8244 7978722 http://zaguan.unizar.es/record/135753/files/texto_completo.pdf Versión publicada 3438553 http://zaguan.unizar.es/record/135753/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:135753 articulos driver 2026-02-17-20:35:50 ARTICLE