CoFe₂O₄ Nanoparticles: Synthesis, Physicochemical Characterization, and Reactive Oxygen Species-mediated Selective Cytotoxicity for Radiotherapy Applications

Abstract

Magnetic spinel ferrite nanoparticles with redox-active surface characteristics have attracted increasing attention as candidate nanomaterials for enhancing radiation-mediated therapeutic response. This study involved the creation of CoFe₂O₄ nanoparticles through a precisely managed chemical co-precipitation approach, followed by thermal annealing to obtain structurally stable inverse spinel nanostructures. The formation of a phase-pure cubic spinel lattice was confirmed by X-ray diffraction and Raman spectroscopy, whereas electron microscopy revealed predominantly spherical nanoparticles with sizes in the range of 20–40 nm. Nitrogen adsorption–desorption analysis demonstrated mesoporous surface characteristics with specific surface area values between 42 and 73 m ² /g, supporting enhanced nanoparticle–cell interaction. The incorporation of redox-active Co ² ⁺ and Fe ³ ⁺ species into the spinel lattice was validated by X-ray photoelectron spectroscopy. Biological assessments utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay indicated concentration-dependent cytotoxicity against MCF-7 breast cancer lines; however, normal L929 fibroblasts retained comparatively higher viability, suggesting targeted action. The observed cytotoxic behavior is attributed to reactive oxygen species-mediated mitochondrial dysfunction induced by transition-metal-dependent redox activity. In addition, antioxidant activity measured using 2,2 diphenyl-1-picrylhydrazyl assay confirmed concentration-dependent radical scavenging behavior, supporting the redox-modulating capability of the synthesized nanoparticles. The combined structural stability, mesoporous surface architecture, and ROS-mediated selective cytotoxic response suggest that CoFe₂O₄ nanoparticles may serve as promising ferrite-based candidate nanomaterials for nanoparticle-assisted radiotherapy applications. These findings support further investigation of mixed-metal ferrite nanoparticles as potential radiosensitizing agents under clinically relevant fractionated radiation dose conditions.