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

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 m2/g, supporting enhanced nanoparticle-cell interaction. The incorporation of redox-active Co2⁺ and Fe3⁺ 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.