{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:14:49Z","timestamp":1792077289163,"version":"4.4.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Office of the Ministry of Higher Education, Science, Research and Innovation","award":["6501.0207\/8434"],"award-info":[{"award-number":["6501.0207\/8434"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The rising global incidence of hepatocellular carcinoma demands innovative therapeutic strategies. This study explores the enhanced anticancer potential of magnesium-doped copper oxide (Mg-doped CuO) nanoparticles, which were synthesized to improve upon the properties of undoped CuO nanoparticles. Mg-doped CuO nanoparticles with doping concentrations ranging from 1% to 5% were prepared using the co-precipitation method and thoroughly characterized by SEM, EDS, and FTIR. Their biological activity was evaluated against HepG2 liver cancer cells and normal human fibroblast cells. The MTT assay demonstrated a significant, concentration-dependent increase in cytotoxicity for Mg-doped CuO nanoparticles compared to undoped CuO, with the 3% Mg-doped CuO formulation showing the greatest potency (IC50 = 21.99 \u00b5g\/mL at 48 h). Cell cycle analysis revealed that treatment with Mg-doped CuO nanoparticles, particularly at 3% and 5% doping concentrations, induced a substantial G2\/M phase arrest, indicating a mechanism of action involving the disruption of cell division. Furthermore, all Mg-doped CuO nanoparticles exhibited markedly higher IC50 values in normal fibroblasts, confirming a favorable selective toxicity towards cancer cells. Apoptosis was identified as a key cell death pathway through acridine orange\/propidium iodide staining. These results conclusively show that magnesium doping significantly augments the selective anticancer efficacy of CuO nanoparticles via cell cycle arrest and apoptosis induction, presenting a highly promising nanomaterial targeted liver cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms27041647","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:15:54Z","timestamp":1770624954000},"page":"1647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis and Characterization of Mg-Doped CuO Nanoparticles and Their Enhanced Anticancer Efficacy Against HepG2 Liver Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Chanachon","family":"Supha","sequence":"first","affiliation":[{"name":"Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-4764","authenticated-orcid":false,"given":"Ramzan","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Department of Applied Biology, School of Biological Sciences, University of Science and Technology Meghalaya (USTM), Techno City 793101, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vichugorn","family":"Wattayagorn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8294-9997","authenticated-orcid":false,"given":"Sirikanjana","family":"Thongmee","sequence":"additional","affiliation":[{"name":"Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Research Unit of Applied Physics for Agriculture and Medicine: APAM, Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3072-1733","authenticated-orcid":false,"given":"Pramote","family":"Chumnanpuen","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"},{"name":"KUSynBio Special Research Incubator Unit, Kasetsart University International College (KUIC), Kasetsart University, Bangkok 10900, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gabbia, D., and De Martin, S. (2024). Insights into hepatocellular carcinoma: From pathophysiology to novel therapies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084188"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"015011","DOI":"10.1088\/2053-1591\/abd666","article-title":"Green synthesis of CuO NPs, characterization and their toxicity potential against HepG2 cells","volume":"8","author":"Liu","year":"2021","journal-title":"Mater. Res. Express"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"135756","DOI":"10.1016\/j.molstruc.2023.135756","article-title":"Synthesis and characterization of cerium, silver and copper oxide nanoparticles and their anticancer potential of hepatocellular carcinoma HepG2 cancer cells","volume":"1288","author":"Younas","year":"2023","journal-title":"J. Mol. Struct."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Srithongkul, N., Imboon, T., Chumnanpuen, P., Harnkit, N., Wattayagorn, V., Ghosh, S., Chotikaprakhan, S., and Thongmee, S. (2025). Study of Anticancer Applications of Ag\/Er co-doped ZnO Nanostructures as Potential Candidate Nanomedicine. E3S Web of Conferences, EDP Sciences.","DOI":"10.1051\/e3sconf\/202561905002"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102585","DOI":"10.1016\/j.jksus.2023.102585","article-title":"Protocatechuic acid mitigates CuO nanoparticles-induced toxicity by strengthening the antioxidant defense system and suppressing apoptosis in liver cells","volume":"35","author":"Ahamed","year":"2023","journal-title":"J. King Saud. Univ.-Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15477","DOI":"10.1038\/s41598-025-97395-4","article-title":"Unveiling the potency of ZnO and CuO nanocomposites in combating hepatocellular carcinoma by inducing cell death and suppressing migration","volume":"15","author":"Allam","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00432-024-05641-5","article-title":"Unveiling the promising anticancer effect of copper-based compounds: A comprehensive review","volume":"150","author":"Abdolmaleki","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.sjbs.2020.12.006","article-title":"Manganese-doped cerium oxide nanocomposite as a therapeutic agent for MCF-7 adenocarcinoma cell line","volume":"28","author":"Atif","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1007\/s10924-024-03255-z","article-title":"Investigating the anticancer and antioxidant potentials of a polymer-grafted sodium alginate composite embedded with CuO and TiO2 Nanoparticles","volume":"32","author":"Nemr","year":"2024","journal-title":"J. Polym. Environ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7740","DOI":"10.1021\/cr400295a","article-title":"Chemical basis of interactions between engineered nanoparticles and biological systems","volume":"114","author":"Mu","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7487","DOI":"10.1016\/j.ceramint.2013.12.099","article-title":"Influence of Mg doping level on morphology, optical, electrical properties and antibacterial activity of ZnO nanostructures","volume":"40","author":"Iqbal","year":"2014","journal-title":"Ceram. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20230063","DOI":"10.1515\/gps-2023-0063","article-title":"In vitro anti-cancer and antimicrobial effects of manganese oxide nanoparticles synthesized using the Glycyrrhiza uralensis leaf extract on breast cancer cell lines","volume":"12","author":"Althobiti","year":"2023","journal-title":"Green Process. Synth."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"055935","DOI":"10.1088\/1402-4896\/acccba","article-title":"Impact of Mg-doping on the structural, optical, and magnetic properties of CuO nanoparticles and their antibiofilm activity","volume":"98","author":"Adnan","year":"2023","journal-title":"Phys. Scr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100250","DOI":"10.1016\/j.hybadv.2024.100250","article-title":"Synthesis of copper oxide (CuO) via coprecipitation method: Tailoring structural and optical properties of CuO nanoparticles for optoelectronic device applications","volume":"6","author":"Ali","year":"2024","journal-title":"Hybrid Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9944","DOI":"10.48048\/wjst.2021.9944","article-title":"Facile synthesis of spherical flake-shaped CuO nanostructure and its characterization towards solar cell application","volume":"18","author":"Pauldurai","year":"2021","journal-title":"Walailak J. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e42557","DOI":"10.1016\/j.heliyon.2025.e42557","article-title":"Green nanoparticles synthesized from damask rose petals: Evaluation of their antioxidant, antimicrobial, anti-diabetic, anti-Alzheimer, and photocatalytic properties","volume":"11","author":"Alizadeh","year":"2025","journal-title":"Heliyon"},{"key":"ref_17","first-page":"51","article-title":"Endocytosis and exocytosis of nanoparticles in mammalian cells","volume":"9","author":"Oh","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chantawannakul, J., Chatpattanasiri, P., Wattayagorn, V., Kongsema, M., Noikaew, T., and Chumnanpuen, P. (2021). Virtual screening for biomimetic anti-cancer peptides from Cordyceps militaris putative pepsinized peptidome and validation on colon cancer cell line. Molecules, 26.","DOI":"10.3390\/molecules26195767"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10876-025-02950-8","article-title":"Sustainable Synthesis of Cu\/Cu2O Yolk-Shell Nanostructures: Characterizations, DPPH\u2022 Interaction, Antibacterial Properties, and Cytotoxicity Against HepG2 Cells","volume":"37","author":"Anbalagan","year":"2026","journal-title":"J. Clust. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/smll.200801220","article-title":"Surface characteristics, copper release, and toxicity of nano-and micrometer-sized copper and copper (II) oxide particles: A cross-disciplinary study","volume":"5","author":"Midander","year":"2009","journal-title":"Small"},{"key":"ref_21","first-page":"2641","article-title":"Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells","volume":"7","author":"Wang","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Adnan, R.M., Mezher, M., Abdallah, A.M., Awad, R., and Khalil, M.I. (2022). Synthesis, characterization, and antibacterial activity of Mg-doped CuO nanoparticles. Molecules, 28.","DOI":"10.3390\/molecules28010103"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e70003","DOI":"10.1002\/metm.70003","article-title":"Advancements in Magnesium Applications, Biocompatible Implants to Nanoparticles in Medicine and Biomedical Innovations","volume":"2","author":"Mubeen","year":"2025","journal-title":"MetalMat"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s11671-018-2532-3","article-title":"Properties of zinc oxide nanoparticles and their activity against microbes","volume":"13","author":"Siddiqi","year":"2018","journal-title":"Nanoscale Res. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrd2803","article-title":"Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach?","volume":"8","author":"Trachootham","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101669","DOI":"10.1016\/j.jksus.2021.101669","article-title":"Assessment of green and chemically synthesized copper oxide nanoparticles against hepatocellular carcinoma","volume":"33","author":"Shafiq","year":"2021","journal-title":"J. King Saud. Univ.-Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/35041687","article-title":"Oxidants, oxidative stress and the biology of ageing","volume":"408","author":"Finkel","year":"2000","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19507","DOI":"10.1073\/pnas.1318431110","article-title":"Bioavailable copper modulates oxidative phosphorylation and growth of tumors","volume":"110","author":"Ishida","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pfeffer, C.M., and Singh, A.T. (2018). Apoptosis: A target for anticancer therapy. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19020448"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrd4002","article-title":"Modulation of oxidative stress as an anticancer strategy","volume":"12","author":"Gorrini","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1021\/es902987d","article-title":"Stability and aggregation of metal oxide nanoparticles in natural aqueous matrices","volume":"44","author":"Keller","year":"2010","journal-title":"Environ. Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.watres.2007.11.036","article-title":"Stability of commercial metal oxide nanoparticles in water","volume":"42","author":"Zhang","year":"2008","journal-title":"Water Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.taap.2009.03.026","article-title":"Metallothionein protection of cadmium toxicity","volume":"238","author":"Klaassen","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1647\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:22:28Z","timestamp":1770625348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/4\/1647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,8]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27041647"],"URL":"https:\/\/doi.org\/10.3390\/ijms27041647","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,8]]}}}