Nickel Ferrite Nanoparticles Potentiate the Anticancer Effects of Doxorubicin in Human Lung A549 Cancer Cells

Nickel ferrite (NiFe₂O₄) nanoparticles, a class of Fe-based magnetic nanoparticles (MNPs), have attracted increasing attention for cancer therapy because of their biocompatibility, magnetic responsiveness, and potential to enhance the efficacy of chemotherapeutic drugs. This study aimed to investigate the in vitro synergistic anticancer effect of NiFe₂O₄ nanoparticles in combination with doxorubicin (Dox) on human lung adenocarcinoma A549 cells. NiFe₂O₄ nanoparticles were synthesized and characterized by X-ray diffraction (XRD), confirming spinel crystallinity; scanning electron microscopy (SEM), revealing nanorod morphology; and energy-dispersive X-ray spectroscopy (EDX), confirming elemental composition. X-ray photoelectron microscope (XPS), Raman scattering, and also Brunauer-Emmett-Teller (BET) analysis were performed to understand the surface. Cytotoxicity was assessed by WST-8 assay, and apoptosis induction was evaluated by mRNA expression analysis of CASP6, BAX, and BCL2 using RT-qPCR. NiFe₂O₄ nanoparticles alone exhibited dose-dependent cytotoxicity with an IC₅₀ of 69.59 μg/mL. When combined with subtoxic Dox (1.485 μM), a strong synergistic effect was observed, reducing the combination IC₅₀ to 15.39 μg/mL. Gene expression results indicated that the combination treatment significantly upregulated CASP6 and BAX, while downregulating BCL2, confirming enhanced apoptosis. NiFe₂O₄ nanoparticles potentiate the anticancer activity of doxorubicin in A549 cells at lower doses, suggesting a promising strategy to enhance efficacy while potentially reducing chemotherapeutic side effects.