000135753 001__ 135753 000135753 005__ 20240705134227.0 000135753 0247_ $$2doi$$a10.1021/acsami.4c04336 000135753 0248_ $$2sideral$$a138649 000135753 037__ $$aART-2024-138649 000135753 041__ $$aeng 000135753 100__ $$0(orcid)0000-0002-1791-0188$$aBonet-Aleta, Javier$$uUniversidad de Zaragoza 000135753 245__ $$aNanomedicine targeting cuproplasia in cancer: labile copper sequestration using polydopamine particles blocks tumor growth in vivo through altering metabolism and redox homeostasis 000135753 260__ $$c2024 000135753 5060_ $$aAccess copy available to the general public$$fUnrestricted 000135753 5203_ $$aCopper 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. 000135753 536__ $$9info:eu-repo/grantAgreement/EC/H2020/742684/EU/Catalytic Dual-Function Devices Against Cancer/CADENCE$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 742684-CADENCE$$9info:eu-repo/grantAgreement/ES/ISCIII DTS21-00130$$9info:eu-repo/grantAgreement/ES/ISCIII/PI19-01007$$9info:eu-repo/grantAgreement/ES/MICINN/PDC2022-133866-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-127847OB-I00$$9info:eu-repo/grantAgreement/ES/UZ/ICTS NANBIOSIS-CIBER-BBN 000135753 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000135753 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000135753 700__ $$aEncinas-Giménez, Miguel$$uUniversidad de Zaragoza 000135753 700__ $$aOi, Miku 000135753 700__ $$aPezacki, Aidan T. 000135753 700__ $$0(orcid)0000-0002-6873-5244$$aSebastián, Víctor$$uUniversidad de Zaragoza 000135753 700__ $$ade Martino, Alba 000135753 700__ $$aMartín Pardillos, Ana$$uUniversidad de Zaragoza 000135753 700__ $$0(orcid)0000-0003-4160-9720$$aMartín-Duque, Pilar$$uUniversidad de Zaragoza 000135753 700__ $$0(orcid)0000-0002-4546-4111$$aHueso, José L.$$uUniversidad de Zaragoza 000135753 700__ $$aChang, Christopher J. 000135753 700__ $$0(orcid)0000-0002-8701-9745$$aSantamaría, Jesús$$uUniversidad de Zaragoza 000135753 7102_ $$11013$$2275$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Estomatología 000135753 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química 000135753 7102_ $$15005$$2790$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Tecnologi. Medio Ambiente 000135753 773__ $$g16, 23 (2024), 29844-29855$$pACS appl. mater. interfaces$$tACS applied materials & interfaces$$x1944-8244 000135753 8564_ $$s7978722$$uhttps://zaguan.unizar.es/record/135753/files/texto_completo.pdf$$yVersión publicada 000135753 8564_ $$s3438553$$uhttps://zaguan.unizar.es/record/135753/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000135753 909CO $$ooai:zaguan.unizar.es:135753$$particulos$$pdriver 000135753 951__ $$a2024-07-05-12:55:55 000135753 980__ $$aARTICLE