{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T22:17:16Z","timestamp":1771539436435,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["20-74-10087"],"award-info":[{"award-number":["20-74-10087"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The link between copper metabolism and tumor progression motivated us to use copper chelators for suppression of tumor growth. We assume that silver nanoparticles (AgNPs) can be used for lowering bioavailable copper. Our assumption is based on the ability of Ag(I) ions released by AgNPs in biological media and interfere with Cu(I) transport. Intervention of Ag(I) into copper metabolism leads to the replacement of copper by silver in ceruloplasmin and the decrease in bioavailable copper in the bloodstream. To check this assumption, mice with ascitic or solid Ehrlich adenocarcinoma (EAC) were treated with AgNPs using different protocols. Copper status indexes (copper concentration, ceruloplasmin protein level, and oxidase activity) were monitored to assess copper metabolism. The expression of copper-related genes was determined by real-time PCR in the liver and tumors, and copper and silver levels were measured by FAAS. Intraperitoneal AgNPs treatment beginning on the day of tumor inoculation enhanced mice survival, reduced the proliferation of ascitic EAC cells, and suppressed the activity of HIF1\u03b1, TNF-\u03b1 and VEGFa genes. Topical treatment by the AgNPs, which was started together with the implantation of EAC cells in the thigh, also enhanced mice survival, decreased tumor growth, and repressed genes responsible for neovascularization. The advantages of silver-induced copper deficiency over copper chelators are discussed.<\/jats:p>","DOI":"10.3390\/pharmaceutics15041099","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T01:05:26Z","timestamp":1680138326000},"page":"1099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Influence of Silver Nanoparticles on the Growth of Ascitic and Solid Ehrlich Adenocarcinoma: Focus on Copper Metabolism"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1959-7110","authenticated-orcid":false,"given":"Daria N.","family":"Magazenkova","sequence":"first","affiliation":[{"name":"Research Center of Advanced Functional Materials and Laser Communication Systems, Institute of Advanced Data Transfer Systems, ITMO University, 197101 St. Petersburg, Russia"},{"name":"Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, 195251 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina A.","family":"Skomorokhova","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, Research Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-4126","authenticated-orcid":false,"given":"Mohammad Al","family":"Farroukh","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Scientific Institution, Saint Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3352-8197","authenticated-orcid":false,"given":"Maria S.","family":"Zharkova","sequence":"additional","affiliation":[{"name":"Department of General Pathology and Pathophysiology, Research Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zena M.","family":"Jassem","sequence":"additional","affiliation":[{"name":"Research Center of Advanced Functional Materials and Laser Communication Systems, Institute of Advanced Data Transfer Systems, ITMO University, 197101 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria E.","family":"Rekina","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, 195251 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5168-2801","authenticated-orcid":false,"given":"Olga V.","family":"Shamova","sequence":"additional","affiliation":[{"name":"Department of General Pathology and Pathophysiology, Research Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0958-2812","authenticated-orcid":false,"given":"Ludmila V.","family":"Puchkova","sequence":"additional","affiliation":[{"name":"Research Center of Advanced Functional Materials and Laser Communication Systems, Institute of Advanced Data Transfer Systems, ITMO University, 197101 St. Petersburg, Russia"},{"name":"Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, 195251 St. Petersburg, Russia"},{"name":"Department of Molecular Genetics, Research Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5623-2156","authenticated-orcid":false,"given":"Ekaterina Y.","family":"Ilyechova","sequence":"additional","affiliation":[{"name":"Research Center of Advanced Functional Materials and Laser Communication Systems, Institute of Advanced Data Transfer Systems, ITMO University, 197101 St. Petersburg, Russia"},{"name":"Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, 195251 St. Petersburg, Russia"},{"name":"Department of Molecular Genetics, Research Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1093\/qjmed\/hcg114","article-title":"Abdominal Malignancies in Patients with Wilson\u2019s Disease","volume":"96","author":"Walshe","year":"2003","journal-title":"QJM"},{"key":"ref_2","first-page":"910","article-title":"Copper-overload causes cancer? The LEC rat: A model for human hepatitis, liver cancer, and much more","volume":"13","author":"Powell","year":"1994","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2353\/ajpath.2006.050312","article-title":"Consequences of Copper Accumulation in the Livers of the Atp7b-\/- (Wilson Disease Gene) Knockout Mice","volume":"168","author":"Huster","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ctrv.2008.07.004","article-title":"Elevated Copper and Oxidative Stress in Cancer Cells as a Target for Cancer Treatment","volume":"35","author":"Gupte","year":"2009","journal-title":"Cancer Treat. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"129S","DOI":"10.2967\/jnumed.107.045914","article-title":"Molecular Imaging of Hypoxia","volume":"49","author":"Krohn","year":"2008","journal-title":"J. Nucl. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1124\/mol.108.051516","article-title":"Copper Regulation of Hypoxia-Inducible Factor-1 Activity","volume":"75","author":"Feng","year":"2009","journal-title":"Mol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1039\/C8MT00280K","article-title":"Copper Affects the Binding of HIF-1\u03b1 to the Critical Motifs of Its Target Genes","volume":"11","author":"Wu","year":"2019","journal-title":"Metallomics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.mam.2009.12.004","article-title":"The Warburg Effect and Mitochondrial Stability in Cancer Cells","volume":"31","author":"Gogvadze","year":"2010","journal-title":"Mol. Asp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.biomaterials.2009.10.009","article-title":"The Stimulation of Angiogenesis and Collagen Deposition by Copper","volume":"31","author":"Bordeleau","year":"2010","journal-title":"Biomaterials"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1039\/C4MT00052H","article-title":"Copper-Dependent and -Independent Hypoxia-Inducible Factor-1 Regulation of Gene Expression","volume":"6","author":"Zhang","year":"2014","journal-title":"Metallomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"34158","DOI":"10.18632\/oncotarget.5779","article-title":"Copper Activates HIF-1\u03b1\/GPER\/VEGF Signalling in Cancer Cells","volume":"6","author":"Rigiracciolo","year":"2015","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000438485","article-title":"Behind the Link between Copper and Angiogenesis: Established Mechanisms and an Overview on the Role of Vascular Copper Transport Systems","volume":"52","author":"Urso","year":"2015","journal-title":"J. Vasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"996S","DOI":"10.1093\/ajcn\/67.5.996S","article-title":"Copper, Lysyl Oxidase, and Extracellular Matrix Protein Cross-Linking","volume":"67","author":"Rucker","year":"1998","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1002\/jcb.21371","article-title":"Paradoxical Roles for Lysyl Oxidases in Cancer\u2014A Prospect","volume":"101","author":"Payne","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.3892\/ijmm.2015.2337","article-title":"The Function and Mechanisms of Action of LOXL2 in Cancer (Review)","volume":"36","author":"Wu","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6836","DOI":"10.1073\/pnas.1817473116","article-title":"ATP7A Delivers Copper to the Lysyl Oxidase Family of Enzymes and Promotes Tumorigenesis and Metastasis","volume":"116","author":"Shanbhag","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s12307-012-0105-z","article-title":"Lysyl Oxidase, Extracellular Matrix Remodeling and Cancer Metastasis","volume":"5","author":"Xiao","year":"2012","journal-title":"Cancer Microenviron."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1158\/0008-5472.CAN-10-1516","article-title":"The HIF-1-Inducible Lysyl Oxidase Activates HIF-1 via the Akt Pathway in a Positive Regulation Loop and Synergizes with HIF-1 in Promoting Tumor Cell Growth","volume":"71","author":"Pez","year":"2011","journal-title":"Cancer Res."},{"key":"ref_19","first-page":"2287","article-title":"Hypoxia-Inducible Factor-1\u03b1 Regulates Epithelial-To-Mesenchymal Transition in Paraquat-Induced Pulmonary Fibrosis by Activating Lysyl Oxidase","volume":"15","author":"Lu","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"126712","DOI":"10.1016\/j.jtemb.2021.126712","article-title":"COMMD1, a Multi-Potent Intracellular Protein Involved in Copper Homeostasis, Protein Trafficking, Inflammation, and Cancer","volume":"65","author":"Weiskirchen","year":"2021","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10495-022-01734-z","article-title":"XIAP as a Multifaceted Molecule in Cellular Signaling","volume":"27","author":"Hanifeh","year":"2022","journal-title":"Apoptosis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/sj.emboj.7600031","article-title":"A Novel Role for XIAP in Copper Homeostasis through Regulation of MURR1","volume":"23","author":"Burstein","year":"2004","journal-title":"EMBO J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.abb.2007.01.033","article-title":"XIAP: Cell Death Regulation Meets Copper Homeostasis","volume":"463","author":"Mufti","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hussain, A.R., Siraj, A.K., Ahmed, M., Bu, R., Pratheeshkumar, P., Alrashed, A.M., Qadri, Z., Ajarim, D., Al-Dayel, F., and Beg, S. (2017). XIAP Over-Expression is an Independent Poor Prognostic Marker in Middle Eastern Breast Cancer and Can be Targeted to Induce Efficient Apoptosis. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3627-4"},{"key":"ref_25","first-page":"919","article-title":"Overexpression of XIAP Expression in Renal Cell Carcinoma Predicts a Worse Prognosis","volume":"30","author":"Mizutani","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.molcel.2006.01.033","article-title":"XIAP is a Copper Binding Protein Deregulated in Wilson\u2019s Disease and Other Copper Toxicosis Disorders","volume":"21","author":"Mufti","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"118867","DOI":"10.1016\/j.bbamcr.2020.118867","article-title":"Getting out What You Put in: Copper in Mitochondria and Its Impacts on Human Disease","volume":"1868","author":"Cobine","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"124888","DOI":"10.1016\/j.jhazmat.2020.124888","article-title":"Exposure to Copper Induces Mitochondria-Mediated Apoptosis by Inhibiting Mitophagy and the PINK1\/Parkin Pathway in Chicken (Gallus Gallus) Livers","volume":"408","author":"Yang","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/j.molcel.2022.05.001","article-title":"Cuproptosis: Cellular and Molecular Mechanisms Underlying Copper-Induced Cell Death","volume":"82","author":"Cobine","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1053\/j.gastro.2018.11.032","article-title":"Activation of Autophagy, Observed in Liver Tissues From Patients with Wilson Disease and From ATP7B-Deficient Animals, Protects Hepatocytes from Copper-Induced Apoptosis","volume":"156","author":"Polishchuk","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper Induces Cell Death by Targeting Lipoylated TCA Cycle Proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/s41392-022-01229-y","article-title":"Copper Homeostasis and Cuproptosis in Health and Disease","volume":"7","author":"Chen","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41568-021-00417-2","article-title":"Connecting Copper and Cancer: From Transition Metal Signalling to Metalloplasia","volume":"22","author":"Ge","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1001\/archneur.1991.00530130050019","article-title":"Initial Therapy of Patients with Wilson\u2019s Disease with Tetrathiomolybdate","volume":"48","author":"Brewer","year":"1991","journal-title":"Arch. Neurol."},{"key":"ref_35","first-page":"1","article-title":"Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: Phase I study","volume":"6","author":"Brewer","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0162-0134(99)00057-4","article-title":"Comparative Mechanism and Toxicity of Tetra- and Dithiomolybdates in the Removal of Copper","volume":"75","author":"Ogra","year":"1999","journal-title":"J. Inorg. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jtra.10045","article-title":"Copper-Lowering Therapy with Tetrathiomolybdate for Cancer and Diseases of Fibrosis and Inflammation","volume":"16","author":"Brewer","year":"2003","journal-title":"J. Trace Elem. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1159\/000106066","article-title":"Phase II Trial of Copper Depletion with Tetrathiomolybdate as an Antiangiogenesis Strategy in Patients with Hormone-Refractory Prostate Cancer","volume":"71","author":"Henry","year":"2006","journal-title":"Oncology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1093\/annonc\/mds654","article-title":"Tetrathiomolybdate-Associated Copper Depletion Decreases Circulating Endothelial Progenitor Cells in Women with Breast Cancer at High Risk of Relapse","volume":"24","author":"Jain","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2217\/mmt-2015-0005","article-title":"Copper Suppression as Cancer Therapy: The Rationale for Copper Chelating Agents in BRAFV600 Mutated Melanoma","volume":"3","author":"Sammons","year":"2016","journal-title":"Melanoma Manag."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1002\/iub.2341","article-title":"Copper Homeostasis: Emerging Target for Cancer Treatment","volume":"72","author":"Li","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.freeradbiomed.2013.02.003","article-title":"The Copper Chelator ATN-224 Induces Peroxynitrite-Dependent Cell Death in Hematological Malignancies","volume":"60","author":"Lee","year":"2013","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.urolonc.2011.04.009","article-title":"A Non-Comparative Randomized Phase II Study of 2 Doses of ATN-224, a Copper\/Zinc Superoxide Dismutase Inhibitor, in Patients with Biochemically Recurrent Hormone-Na\u00efve Prostate Cancer","volume":"31","author":"Lin","year":"2013","journal-title":"Urol. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10844","DOI":"10.1038\/s41598-017-11121-3","article-title":"Bio-Fabrication of Silver Nanoparticles by Phycocyanin, Characterization, in Vitro Anticancer Activity Against Breast Cancer Cell Line and in Vivo Cytotxicity","volume":"7","author":"Hussein","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s00210-018-1558-5","article-title":"Antitumor Activity of Silver Nanoparticles in Ehrlich Carcinoma-Bearing Mice","volume":"391","author":"Rageh","year":"2018","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13223","DOI":"10.1111\/jcmm.15934","article-title":"Biogenic Silver\/Silver Chloride Nanoparticles Inhibit Human Glioblastoma Stem Cells Growth in Vitro and Ehrlich Ascites Carcinoma Cell growth in Vivo","volume":"24","author":"Kabir","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8909","DOI":"10.1038\/s41598-022-12974-z","article-title":"Biogenic Silver\/Silver Chloride Nanoparticles Inhibit Human Cancer Cells Proliferation in Vitro and Ehrlich Ascites Carcinoma Cells Growth in Vivo","volume":"12","author":"Kabir","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1049\/nbt2.12075","article-title":"Hypnea Musciformis-Mediated Ag\/AgCl-NPs Inhibit Pathogenic Bacteria, HCT-116 and MCF-7 Cells\u2019 Growth in Vitro and Ehrlich Ascites Carcinoma Cells in Vivo in Mice","volume":"16","author":"Ghose","year":"2022","journal-title":"IET Nanobiotechnology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Puchkova, L.V., Broggini, M., Polishchuk, E.V., Ilyechova, E.Y., and Polishchuk, R.S. (2019). Silver Ions as a Tool for Understanding Different Aspects of Copper Metabolism. Nutrients, 11.","DOI":"10.3390\/nu11061364"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"131093","DOI":"10.1016\/j.jhazmat.2023.131093","article-title":"Chemical Background of Silver Nanoparticles Interfering with Mammalian Copper Metabolism","volume":"451","author":"Skvortsov","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1039\/C4MT00107A","article-title":"The Effects of Silver Ions on Copper Metabolism in Rats","volume":"6","author":"Ilyechova","year":"2014","journal-title":"Metallomics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6561","DOI":"10.2147\/IJN.S117745","article-title":"New Silver Nanoparticles Induce Apoptosis-Like Process in E.coli and Interfere with Mammalian Copper Metabolism","volume":"11","author":"Orlov","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0009-8981(61)90074-2","article-title":"Detection of ceruloplasmin after zone electrophoresis","volume":"6","author":"Owen","year":"1961","journal-title":"Clin. Chim. Acta"},{"key":"ref_54","first-page":"631","article-title":"Two-Stage Method for Purification of Ceruloplasmin Based on Its Interaction with Neomycin","volume":"77","author":"Sokolov","year":"2012","journal-title":"Biochemistry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2147\/NSA.S287658","article-title":"Size-Dependent Bioactivity of Silver Nanoparticles: Antibacterial Properties, Influence on Copper Status in Mice, and Whole-Body Turnover","volume":"13","author":"Skomorokhova","year":"2020","journal-title":"Nanotechnol. Sci. Appl."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1002\/smll.201202120","article-title":"Toxicity of Silver Nanoparticles in Macrophages","volume":"9","author":"Pratsinis","year":"2013","journal-title":"Small"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3581","DOI":"10.1039\/D2EN00402J","article-title":"Shape-Dependent Biological Activity of Spherical and Quasi-Spherical Silver Nanoparticles in E. coli, A549 Cells and Mice","volume":"9","author":"Puchkova","year":"2022","journal-title":"Environ. Sci. Nano"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jtemb.2010.08.002","article-title":"Experimental Switching of Copper Status in Laboratory Rodents","volume":"25","author":"Ilyechova","year":"2011","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"614","DOI":"10.4161\/cbt.24594","article-title":"Non-Hepatic Tumors Change the Activity of Genes Encoding Copper Trafficking Proteins in the Liver","volume":"14","author":"Babich","year":"2013","journal-title":"Cancer Biol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7441","DOI":"10.1158\/1078-0432.CCR-09-1361","article-title":"Antiangiogenic Tetrathiomolybdate Protects against Her2\/Neu-Induced Breast Carcinoma by Hypoplastic Remodeling of the Mammary Gland","volume":"15","author":"Pan","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6410","DOI":"10.1158\/0008-5472.CAN-04-1543","article-title":"Lysyl Oxidase is a Tumor Suppressor Gene Inactivated by Methylation and Loss of Heterozygosity in Human Gastric Cancers","volume":"64","author":"Kaneda","year":"2004","journal-title":"Cancer Res."},{"key":"ref_62","first-page":"263","article-title":"The role of ceruloplasmin in the development of neoplastic processes. Review","volume":"51","author":"Vavilova","year":"2005","journal-title":"Biomeditsinskaia Khimiia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2009S","DOI":"10.3945\/ajcn.2009.27230E","article-title":"Methods of Assessment of Copper Status in Humans: A Systematic Review","volume":"89","author":"Harvey","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jtemb.2016.12.013","article-title":"Ceruloplasmin Gene Expression Profile Changes in the Rat Mammary Gland during Pregnancy, Lactation and Involution","volume":"43","author":"Platonova","year":"2017","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_65","first-page":"65","article-title":"Cellular Energetics as a Target for Tumor Cell Elimination","volume":"81","author":"Maximchik","year":"2016","journal-title":"Biochemistry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nchembio.72","article-title":"Mechanisms for Copper Acquisition, Distribution and Regulation","volume":"4","author":"Kim","year":"2008","journal-title":"Nat. Chem. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1161\/CIRCULATIONAHA.117.030816","article-title":"Heart Failure Stimulates Tumor Growth by Circulating Factors","volume":"138","author":"Meijers","year":"2018","journal-title":"Circulation"},{"key":"ref_68","first-page":"RA48","article-title":"Ceruloplasmin\u2014acute-phase reactant or endogenous antioxidant? The case of cardiovascular disease","volume":"11","author":"Giurgea","year":"2005","journal-title":"Med. Sci. Monit."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"G356","DOI":"10.1152\/ajpgi.90632.2008","article-title":"Deletion of Hepatic Ctr1 Reveals Its Function in Copper Acquisition and Compensatory Mechanisms for Copper Homeostasis","volume":"296","author":"Kim","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ilyechova, E.Y., Tsymbalenko, N.V., and Puchkova, L.V. (2017). The Role of Subcutaneous Adipose Tissue in Supporting the Copper Balance in Rats with a Chronic Deficiency in Holo-Ceruloplasmin. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175214"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s00018-002-8519-2","article-title":"Structure to Function Relationships in Ceruloplasmin: A \u2018Moonlighting\u2019 Protein","volume":"59","author":"Bielli","year":"2002","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.fsi.2018.08.043","article-title":"Ceruloplasmin, a Moonlighting Protein in Fish","volume":"82","author":"Das","year":"2018","journal-title":"Fish Shellfish. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s007750050018","article-title":"The X-ray Structure of Human Serum Ceruloplasmin at 3.1 Angstrom: Nature of the Copper Centres","volume":"1","author":"Zaitseva","year":"1996","journal-title":"J. Biol. Inorg. Chem."},{"key":"ref_74","unstructured":"Card, G.L., Zaitsev, V.N., and Lindley, P.F. (2023, January 10). X-ray Crystal Structure of Human Ceruloplasmin at 3.0 Angstroms. PDB. Available online: https:\/\/www.wwpdb.org\/pdb?id=pdb_00001kcw."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zatulovskiy, E., Samsonov, S., and Skvortsov, A. (2007). Docking Study on Mammalian CTR1 Copper Importer Motifs. BMC Syst. Biol., 1.","DOI":"10.1186\/1752-0509-1-S1-P54"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Ramos, D., Mar, D., Ishida, M., Vargas, R., Gaite, M., Montgomery, A., and Linder, M.C. (2016). Mechanism of Copper Uptake from Blood Plasma Ceruloplasmin by Mammalian Cells. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149516"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"111424","DOI":"10.1016\/j.jinorgbio.2021.111424","article-title":"Ceruloplasmin as a Source of Cu for a Fungal Pathogen","volume":"219","author":"Besold","year":"2021","journal-title":"J. Inorg. Biochem."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/4\/1099\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:06:18Z","timestamp":1760123178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/4\/1099"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,29]]},"references-count":77,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["pharmaceutics15041099"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15041099","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,29]]}}}