# Synthesis, characterization of Mg doped CuFe2O4 nanoparticles for potential anticancer applications

**Authors:** Mohamed Ali, Nabila Zein, M. A. Abdo, Gehan Adel, Basel Sitohy

PMC · DOI: 10.1038/s41598-026-41540-0 · 2026-03-05

## TL;DR

This study shows that Mg-doped copper ferrite nanoparticles can effectively kill cancer cells by inducing apoptosis and DNA damage.

## Contribution

The novel contribution is the synthesis and evaluation of Mg-doped CuFe2O4 nanoparticles with optimized properties for anticancer activity.

## Key findings

- Cu0.5Mg0.5Fe2O4 showed the highest cytotoxicity with IC₅₀ values of 17.2 µg/mL and 25.04 µg/mL against PC-3 and Caco-2 cells.
- The nanoparticles induced significant apoptosis (42.08% in PC-3 and 34.95% in Caco-2 cells) through ROS-mediated pathways.
- Gene expression changes indicated mitochondrial-dependent apoptosis via BAX, P53, and Caspase-3 upregulation and Bcl-2 downregulation.

## Abstract

Ferrite nanoparticles (NPs) have emerged as promising candidates for cancer therapy. In this study, Mg-doped copper ferrite NPs, MgₓCu₁₋ₓFe2O4 (x = 0.0, 0.5, and 1.0), were synthesized via a citrate–nitrate combustion method and evaluated for their anticancer potential. Structural and morphological characteristics were analyzed using powder X-ray diffraction, field-emission scanning electron microscopy, and energy-dispersive X-ray spectroscopy. Cytotoxicity against human cancer cell lines was assessed using MTT and flow cytometry assays, along with analyses of reactive oxygen species (ROS) generation and apoptosis. Among the compositions studied, Cu0.5Mg0.5Fe2O4 demonstrated the highest cytotoxic efficacy, with IC₅₀ values of 17.2 ± 0.15 µg/mL (PC-3) and 25.04 ± 0.28 µg/mL (Caco-2). Flow cytometric analysis revealed increased total apoptosis of 42.08% and 34.95% in PC-3 and Caco-2 cells, respectively. Gene expression analysis revealed downregulation of Bcl-2 and Cyclin D and upregulation of BAX, P53, and Caspase-3, indicating ROS-mediated mitochondria-dependent apoptosis. The enhanced anticancer activity of Cu0.5Mg0.5Fe2O4 is attributed to its optimized size, surface charge, and composition, which promote cellular uptake, ROS generation, DNA damage, and interactions with cellular components. These findings highlight the potential of mixed-metal ferrite nanoparticles as effective nanomaterial-based cancer therapeutics.

## Linked entities

- **Genes:** BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], CycD (Cyclin D) [NCBI Gene 32551], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], TP53 (tumor protein p53) [NCBI Gene 7157], Casp3 (caspase 3) [NCBI Gene 12367]

## Full-text entities

- **Genes:** CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}
- **Diseases:** hyperthermia (MESH:D005334), colon carcinoma (MESH:D003110), prostate cancer (MESH:D011471), inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), Cancer (MESH:D009369), lung cancer (MESH:D008175), breast cancer (MESH:D001943), necrosis (MESH:D009336), liver cancer (MESH:D006528), prostate carcinoma (MESH:D011472), FHC (MESH:D024741), Colon cancer (MESH:D015179), Cytotoxicity (MESH:D064420)
- **Chemicals:** ferric nitrate (MESH:C025302), water (MESH:D014867), 5-FU (MESH:D005472), Trizol (MESH:C411644), 2',7'-Dichlorofluorescin diacetate (MESH:C029569), Fe (MESH:D007501), Cu (MESH:D003300), Fe2O3 (MESH:C000499), copper nitrate (MESH:C516433), hydroxyl radicals (MESH:D017665), HA (MESH:D006820), Ferrite (MESH:C001215), singlet oxygen (MESH:D026082), metal (MESH:D008670), O (MESH:D010100), Ammonia (MESH:D000641), CuFe2O4 (MESH:C523076), nitrate (MESH:D009566), magnetite (MESH:D052203), PI (MESH:D010716), EDTA (MESH:D004492), FITC (MESH:D016650), magnesium nitrate (MESH:C018330), C6H8O7 (MESH:D019343), GSH (MESH:D005978), CO2 (MESH:D002245), SYBR Green (MESH:C098022), OH (MESH:C031356), taxanes (MESH:D043823), Mg-O (MESH:D008277), lipid (MESH:D008055), MgFe2O4 (MESH:C016546), PBS (MESH:D007854), gemcitabine (MESH:D000093542), ROS (MESH:D017382), Mg (MESH:D008274), Cu-O (MESH:C030973), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), 1O2 (-), superoxide (MESH:D013481), H2O2 (MESH:D006861), cisplatin (MESH:D002945), doxorubicin (MESH:D004317), spinel (MESH:C111130), MTT (MESH:C070243), cyclodextrin (MESH:D003505), PS (MESH:D010718)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** FHC — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_3688), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), HepG-2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), NCIH441 — Homo sapiens (Human), Lung papillary adenocarcinoma, Cancer cell line (CVCL_1561), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), TK6 — Homo sapiens (Human), Hereditary spherocytosis, Transformed cell line (CVCL_0561), PC-3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), Caco-2/TC7 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0233), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), MDCK — Canis lupus familiaris (Dog), Spontaneously immortalized cell line (CVCL_0422)

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12966289/full.md

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Source: https://tomesphere.com/paper/PMC12966289