Oxidation of ferumoxytol by ionizing radiation releases iron. An electron paramagnetic resonance study

Ferumoxytol (FMX) is an iron oxide nanoparticle that is FDA approved for the treatment of iron deficiency anemia. FMX contains an Fe(3)O(4) core. Currently, the redox chemistry of Fe(3)O(4) nanoparticles remains relatively unexplored. FMX has recently gained interest as an anti-cancer agent. Ionizing radiation (IR) is a treatment modality employed to treat several types of cancer. Utilizing electron paramagnetic resonance (EPR) spectroscopy, we found that the products produced from the radiolysis of water can oxidize the Fe(3)O(4) core of FMX. Because of the limited diffusion of the HO(2)(•) and HO(•) produced, these highly oxidizing species have little direct effect on FMX oxidation. We have determined that H(2)O(2) is the primary oxidant of FMX. In the presence of labile Fe(2+), we found that reducing species generated from the radiolysis of H(2)O are able to reduce the Fe(3+) sites of the Fe(3)O(4) core. Importantly, we also have shown that IR stimulates the release of ferric iron from FMX. Because of its release of iron, FMX may serve as an adjuvant to enhance radiotherapy.