Surface chemical and electronic properties of functionalized Fe3O4 nanoparticles influencing their cytotoxicity

Physico-chemical, electronic and magnetic properties of bare Fe3O4 nanoparticles (NPs) and functionalized NPs (f-NPs) with doxorubicin, tannic acid, curcumin, polyethylene glycol and their mixtures were determined using DLS, XRD, XPS and AES. The cytotoxicity of bare and f-NPs for various cell lines such as normal HEK-293 and cancer HeLa, MDA-MB-231, and MCF-7 was studied by MTT (3–(4,5–Dimethylthiazol–2–yl)–2,5–Diphenyltetrazolium Bromide) assay. Bare and f-NPs exhibited different cytotoxicity dependent on molecules bonding at the surface. Cytotoxicity increases with decreasing hydrodynamic diameter and increasing Zeta potential, increasing content of lattice and adsorbed O2−, carboxyl groups and C vacancies, NH4+ groups, decreasing overlayer thickness, electron charge transfer to oxygen and more nucleophilic character of electron rich surface oxygen. The strongest correlation was observed for hydrodynamic diameter, Fe surface content, overlayer thickness, Zeta-potential, Auger parameters indicating that surface processes and electron charge transfer leading to nucleophilic oxygen contribute mostly to cytotoxicity. Nucleophilic biomolecules may form a variety of covalent modifications with electrophilic adducts and hydrogen bonds with nucleophiles and the suspected predominant mechanism of biomolecule damage can be attributed to electron rich nucleophilic oxygen leading to a very selective C–H bonds cleavage resulting in oxidation of organic chains of biomolecule. © 2024 Elsevier B.V.