# Synthesis and Characterization of Mg-Doped CuO Nanoparticles and Their Enhanced Anticancer Efficacy Against HepG2 Liver Cancer Cells

**Authors:** Chanachon Supha, Ramzan Ahmed, Vichugorn Wattayagorn, Sirikanjana Thongmee, Pramote Chumnanpuen

PMC · DOI: 10.3390/ijms27041647 · 2026-02-08

## TL;DR

This study shows that magnesium-doped copper oxide nanoparticles are more effective at killing liver cancer cells than undoped ones, with minimal harm to normal cells.

## Contribution

The novel contribution is the development of Mg-doped CuO nanoparticles with enhanced selective anticancer activity against HepG2 cells.

## Key findings

- 3% Mg-doped CuO showed highest potency with an IC50 of 21.99 µg/mL against HepG2 cells.
- Mg-doped CuO induced G2/M phase arrest and apoptosis in cancer cells.
- Mg-doped CuO exhibited higher IC50 in normal fibroblasts, showing selective toxicity.

## Abstract

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 µg/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.

## Linked entities

- **Chemicals:** acridine orange (PubChem CID 62344), propidium iodide (PubChem CID 4939)
- **Diseases:** hepatocellular carcinoma (MONDO:0007256), liver cancer (MONDO:0002691)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, CASP7 (caspase 7) [NCBI Gene 840] {aka CASP-7, CMH-1, ICE-LAP3, LICE2, MCH3}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, CAT (catalase) [NCBI Gene 847]
- **Diseases:** Cancer (MESH:D009369), injury to (MESH:D014947), HCC (MESH:D006528), necrosis (MESH:D009336), Cytotoxicity (MESH:D064420), metastasis (MESH:D009362), colorectal cancer (MESH:D015179)
- **Chemicals:** HCl (MESH:D006851), Cu (MESH:D003300), ethanol (MESH:D000431), hydroxyl radicals (MESH:D017665), sodium hydroxide (MESH:D012972), water (MESH:D014867), ZnO (MESH:D015034), Cu2O (MESH:C000520), TRIzol (MESH:C411644), PEG (MESH:D011092), EDTA (MESH:D004492), polymers (MESH:D011108), streptomycin (MESH:D013307), metal (MESH:D008670), AO (MESH:D000165), nitrate (MESH:D009566), formazan (MESH:D005562), O (MESH:D010100), Magnesium (MESH:D008274), DMSO (MESH:D004121), ROS (MESH:D017382), CO2 (MESH:D002245), glutathione (MESH:D005978), lipid (MESH:D008055), MgO (MESH:D008277), OH (MESH:C031356), amphotericin B (MESH:D000666), MTT (MESH:C070243), PI (MESH:D011419), H2O2 (MESH:D006861), superoxide (MESH:D013481), Dopant (-), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), CuO (MESH:C030973), penicillin (MESH:D010406)
- **Species:** Cordyceps militaris (species) [taxon 73501], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** PCS-201-010 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_WT11), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), HepG2 hepatocellular carcinoma — Homo sapiens (Human), Hepatocellular carcinoma, Cancer cell line (CVCL_A1AS), fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), CuO2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940181/full.md

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Source: https://tomesphere.com/paper/PMC12940181