Functionalization of iron oxide nanoparticles with small molecules and the impact on reactive oxygen species generation for potential cancer therapy

Iron oxide nanoparticles (IONPs) and their cytotoxicity via reactive oxygen species (ROS) generation have attracted much attention in the last several years. Recent studies show that alternating magnetic field (AMF) exposure can enhance the production of ROS by IONPs, and these ROS have potential use in therapeutic applications. The aim of this research was to develop iron oxide nanoparticles-based platforms with small molecule coatings and to study impact of the coating on the surface reactivity of the particles. Iron oxide nanoparticles were synthesized by a co-precipitation process and coated with citric acid, sodium phosphate, amino-silane, or dopamine. Physicochemical properties of the particles including hydrodynamic size, amount of coating, and AMF heating ability were investigated. Surface reactivity via ROS generation by the particles was evaluated using a methylene blue decolorization assay with hydrogen peroxide and various AMF exposures. It was demonstrated that in general small molecule coatings decreased surface reactivity of IONPs by inhibiting ROS generation compared to uncoated IONPs. These results indicated that small molecules inhibit the ability to use enhancement of ROS generation, and this is important to consider in the design of these systems for cancer therapy and other therapeutic applications.