Glucose oxidase-decorated iron oxide nanoparticles with controlled reactive oxygen species generation for synergistic cancer therapy

Abstract Magnetic iron oxide nanoparticles (Fe 3 O 4 NPs) have been widely functionalized with various biomolecules to enable targeted and synergistic cancer therapies, employing approaches such as coordination chemistry, polymer coatings, and linker molecules for surface modification. In this study, we developed a simple and effective strategy to functionalize Fe 3 O 4 NPs with glucose oxidase (GO x ) through tannic acid (TA)-mediated surface modification, resulting in Fe 3 O 4 -TA@GO x nanocomposites. The structural and morphological characteristics of the nanosystem were systematically analyzed using UVVis spectrophotometry, Fourier-transform infrared spectroscopy, x-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The Fe 3 O 4 -TA@GO x NPs were shown to generate hydrogen peroxide (H 2 O 2 ) via GO x -catalyzed glucose oxidation, which was subsequently converted into highly reactive hydroxyl radicals ( • OH) through Fenton-like reactions mediated by Fe ions, thereby inducing potent anticancer effects. The selective cytotoxicity of the nanocomposites was evaluated on both normal fibroblast cells (L929) and breast cancer cells (MCF-7), demonstrating the preferential toxicity toward cancer cells. These findings highlighted the potential of Fe 3 O 4 -TA@GO x NPs as a multifunctional nanoplatform for enhanced cancer therapy by integrating chemotherapy, reactive oxygen species (ROS)-based treatment, and starvation therapy.