Enhanced anticancer and biological activities of environmentally friendly Ni/Cu-ZnO solid solution nanoparticles

Abstract

The study investigates the impact of incorporating Ni and Cu into the lattice of ZnO nanoparticles (NPs) to enhance their anticancer and antioxidant properties. Characterization techniques including pXRD, FTIR, UV-visible absorption spectroscopy, FESEM, and EDAX confirm the successful synthesis and structural modifications of Ni/Cu-ZnO NPs. Anticancer activity against breast cancer (MDA) and normal skin (BHK-21) cells reveals dose-dependent cytotoxicity, with Ni/Cu-ZnO NPs exhibiting higher efficacy against MDA cells while being less harmful to BHK-21 cells. Morphological studies corroborate these findings. Additionally, antioxidant assays using TAC, FRAP, and DPPH assay demonstrate the superior antioxidant activity of Ni/Cu-ZnO NPs matched to pure ZnO. Overall, the synergistic effect of Ni and Cu incorporation leads to improved therapeutic potential, making Ni/Cu-ZnO NPs promising candidates for cancer therapy and antioxidant applications. Molecular docking recreations were performed using Auto Dock Vina software to gain more insights and validate the observed biological activities of un-doped ZnO and bi-metal doped ZnO NPs, we investigated the interaction and binding affinities of pure ZnO and bimetallic metal co-doped ZnO for their antioxidant and anticancer studies. Ni/Cu-ZnO have shown good antioxidants and exhibited remarkable anticancer activities.

Keywords: Anticancer; Antioxidant activities; Band gap tuning; Solid solutions; ZnO NPs.

Scheme 1(1, 2)

The schematic representation to produce un-doped and Ni/Cu-ZnO NPs.

Fig. 1

2D and 3D structure of (a) Undoped ZnO (b) Ni/Cu doped ZnO.

Fig. 2

(a): 3D Structure of human peroxiredoxin 5 (PDB ID: 1HD2), (b) Binding interaction pattern of un-doped ZnO, (c) Ni/Cu-ZnO NPs with the active pocket of human peroxiredoxin 5 (3D-view).

Fig. 3

a) 3D Configuration of estrogen receptor α (ERα) (PDB ID: 5GS4, (b) Binding interaction pattern of un-doped ZnO, (c) Ni₂₀Cu₂₀ZnO₆₀ NPs with the active pocket of estrogen receptor α (3D-view).

Fig. 4

(a) 3D Configuration of human peroxiredoxin 5 (PDB ID: 1HD2), (b) Binding interaction types of Ni/Cu-ZnO with the active pocket of human peroxiredoxin 5 (3D-view).

Fig. 5

(a) 3D Structure of estrogen receptor α (ERα) (PDB ID: 5GS4), (b) 3D structure of AKT1 target proteins (PDB ID:7NH5), (c) 3D depiction of the binding contact pattern between Ni₂₀Cu₂₀ZnO₆₀ with the active pocket of estrogen receptor α, (d) Binding contact pattern of Ni₂₀Cu₂₀ ZnO₆₀ with the active pocket of Akt1 target (3D-visualization).

Fig. 6

(a) pXRD spectra, (b) FTIR spectra, (c) absorption spectra, and (d) band gap of pure ZnO, Ni₁₀Cu₁₀ZnO, Ni₂₀Cu₂₀ZnO, and Ni₃₀Cu₃₀ZnO nanoparticles.

Fig. 7

SEM Micrographs of (a) pure ZnO, (b) Ni₁₀Cu₁₀-ZnO₈₀ NPs (10 %), (c) Ni₂₀Cu₂₀-ZnO₆₀ NPs (20 %), (d) Ni₃₀Cu₃₀-ZnO₄₀ NPs (30 %).

Fig. 8

The EDAX spectra of (a) ZnO NPs (b) Ni₁₀Cu₁₀ZnO₈₀ NPs (10 %), (c) Ni₂₀Cu₂₀ ZnO₆₀ NPs (20 %), (d) Ni₃₀Cu₃₀ZnO₄₀ NPs (30 %).

Fig. 9

Anticancer activity of pure ZnO NPs, and Cu/Ni-ZnO NPs versus epithelial breast cancer (MDA) and kidney (BHK-21) skin cell lines. MTT assays showing the dosage dependence of % cell viability results of pure ZnO and Cu/Ni-ZnO NPs (a) MDA (b) BHK-21 cells. MTT assays showing the dosage dependence of % cell toxicity results of pure ZnO and Cu₂₀Ni₂₀ZnO₆₀ NPs (c) MDA and (d) BHK-21 cells. (e) Morphological changes in MDA cells after the 24 h exposure to 120 μg/mL of ZnO and Cu/Ni-ZnO NPs. Whereas, (f) is the morphology change in the BHK-21 cells exposed to 120 μg/mL of pure ZnO and Ni₂₀Cu₂₀-ZnO₆₀ NPs for 24 h.

Fig. 10

Illustrate the antioxidant activity of pure ZnO, and Ni/Cu-ZnO, and the results were assessed with the standard ascorbic acid under the same conditions. The antioxidant activity is determined by the total amount of antioxidants by (a) pure ZnO, (b) Ni/Cu-ZnO NPs, (c) Ferric Reducing antioxidant capacity, and (d) DPPH approach by pure ZnO and Ni/Cu-ZnO NPs.

Fig. 11

Reducing power of pure ZnO and Ni/Cu-ZnO NPs.