DNA-functionalized superparamagnetic Fe₃O₄ nanoparticles: In Vitro antioxidant and anticancer assessment in MCF-7 cancer cells

Magnet-mediated gene therapy has emerged as a promising alternative to conventional viral-based genetic strategies, with superparamagnetic iron oxide nanoparticles (Fe₃O₄NPs) being widely explored as non-viral vectors. Despite their availability for certain transfection applications, their broader biomedical potential remains underutilized. Moreover, ethical concerns surrounding human DNA limit translational research, making fish DNA a viable substitute. This study aimed to synthesize DNA-coated Fe₃O₄ nanoparticles (DMn) and further develop a Metformin (MRN)-conjugating DNA–Fe₃O₄ nanoconjugate (MDMn), evaluating their structural features, antioxidant activity, and anticancer potential against MCF-7 breast cancer cells. The synthesized DMn exhibited quasi-spherical morphology (90.4 nm) with a Zeta-potential of –42.20 mV, ensuring colloidal stability. Superparamagnetism was confirmed by the absence of hysteresis. FTIR, FESEM, AFM, and XRD validated DNA coating and decreased crystallinity. Docking studies revealed strong binding between MRN and DNA-Fe₃O₄NPs. Drug release was accelerated from MDMn (109 ± 0.05 % in 8 h) compared to pure MRN (110 ± 0.47 % in 26 h). Biologically, MDMn exhibited notable antioxidant activity (32.41 ± 1.62 % DPPH scavenging) and pronounced, dose-dependent cytotoxicity against MCF-7 cells, achieving 85.47 ± 1.62 % inhibition at 24 h, with a calculated IC₅₀ value of 28.47 ± 1.59 μM. DNA-functionalized Fe₃O₄ nanoparticles, especially MRN-conjugate MDMn, represent a promising non-viral therapeutic platform with potential for targeted breast cancer treatment.