Abstract
Comparing chemically produced zinc oxide nanoparticles (CSZnO-NPs) with green synthetized zinc oxide nanoparticles (ZnO-NPs) made using based red yeast rice (RRY) extract as a reducing and stabilising agent, this study looked at the anticancer potential of Zinc oxide NPs against liver cancer cell line. Zinc acetate dihydrate and sodium hydroxide were utilised as precursors in the chemical synthesis process. The ZnO-NPs that were biosynthesised had flower shapes and an average particle size of 22.1 ± 4.3 nm, as determined by FESEM. In contrast, the CSZnO-NPs had bigger, more irregular structures with a mean size of 37.6 ± 5.1 nm. A spectroscopic analysis of UV-VIS nanoparticles (300–800 nm) revealed unique absorption peaks, while XRD confirmed their crystal structures. Hep-G2 liver cancer cells were used to assess anticancer activity. The cytotoxicity of the green ZnO nanoflowers was much greater than that of the CSZnO-NPs, with an IC₅₀ value of 17.35 µg/mL instead of 22.68 µg/mL. In addition, molecular docking showed that stable complexes (binding energy: -7.18 kcal/mol; Ki: 5.43 µM) were generated by hydrogen bonding with LYS248, HIS179, PRO249, and LEO180 (bond distances: 2.3–3.3 Å) when ZnO nanoflowers were conjugated with the 3HB5 ligand. These results indicate that ZnO-NPs mediated by red yeast rice offer a more environmentally friendly and long-term viable option for treating liver cancer than traditional chemical production methods. Moreover, they show a quantitatively superior anticancer impact.
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Acknowledgements
The authors appreciation to the University of Technology- Iraq for their support. The authors extend their appreciation to the Ongoing Research Funding Program (ORF-2026-971), King Saud University, Riyadh, Saudi Arabia, for funding this research. Also, the authors extend their appreciation to the fundamental Research Grant Scheme (FRGS), grant number FRGS/1/2024/STG05/UKM/01/2 funded by the Ministry of Higher Education (MOHE), Malaysia Universiti Kebangsaan Malaysia.
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A.J.J., M.S.J., and M.R.Y, Writing Original, Methodology, Investigation, Visualization, Data curation and Formal examination. A.J.J., M.S.J., and M.R.Y: Main Concept, Data interpretation, and supervision. A.J.J., M.S.J., M.R.Y, B. A. T., A. A. A., N. M. S., M. F. A., A.B.I and A. A. S.: Writing-review and editing. All authors reviewed the manuscript.
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Jasim, A.J., Yusop, M.R., Taha, B.A. et al. Sustainable development of novel zinc oxide nano flowers mediated red yeast rice for control of hepatocellular carcinoma. Sci Rep (2026). https://doi.org/10.1038/s41598-025-33746-5
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DOI: https://doi.org/10.1038/s41598-025-33746-5