Superparamagnetic Iron Oxide Nanoparticles as Novel X-ray Enhancer for Low-Dose Radiation Therapy

Superparamagnetic iron oxide nanoparticles (SPIONs) with a mixed phase composition (gamma-Fe2O3)(1-x)(Fe3O4)(x) and sizes between 9 and 20 nm were synthesized via coprecipitation and were either left uncoated or subsequently surface-stabilized with citrate or malate anions. The sizes, morphology, surface chemistry, and magnetic properties of the nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and superconducting quantum interference device measurements, respectively. Cellular uptake and intracellular distribution in normal tissue and tumor cells were verified by TEM images. X-ray-induced changes of the oxidation state and site geometries of surface iron ions of uncoated and citrate-coated SPIONs were explored by collecting Fe K-edge X-ray absorption spectroscopy data. The potential applicability of citrate- and malate-coated SPIONs as an X-ray enhancer for radiation cancer therapy was substantiated by their drastic enhancement of the concentration of reactive oxygen species (ROS) in X-ray irradiated tumor cells.