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

Abstract

Ferumoxytol (FMX) is an iron oxide nanoparticle that is FDA approved for the treatment of iron deficiency anemia. FMX contains an Fe3O4 core. Currently, the redox chemistry of Fe3O4 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 Fe3O4 core of FMX. Because of the limited diffusion of the HO2• and HO• produced, these highly oxidizing species have little direct effect on FMX oxidation. We have determined that H2O2 is the primary oxidant of FMX. In the presence of labile Fe2+, we found that reducing species generated from the radiolysis of H2O are able to reduce the Fe3+ sites of the Fe3O4 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.

Magnetite nanoparticles as a kinetically favorable source of iron to enhance GBM response to chemoradiosensitization with pharmacological ascorbate

“…The Fe 3 O 4 core of FMX is a high-spin Fe complex (2Fe 3+ : 1Fe 2+ ) where the Fe 3+ sites are readily detectable by EPR spectroscopy with a concentration-dependent peak at g ≈ 2 ( Figs. S2A and B ) [ 22 ]. Incubating FMX with AscH − at 25 °C with a continuous flow of atmospheric oxygen showed a 23% reduction of FMX concentration within 2 h and 50% reduction 24 h ( Fig.1D , Fig.…”

“…The subsequent species produced, primarily O 2 ●- and H 2 O 2 , may also act in a feed forward manner to decompose the Fe 3 O 4 core because they can readily react with redox-active metals [ 9 , 10 ]. The O 2 •- generated may reduce Fe 3+ , while H 2 O 2 can oxidize Fe 2+ sites of FMX [ 22 ]; however, the reaction between Asc ●- and O 2 ●- to produce H 2 O 2 is more likely. Thus, adding AscH − to FMX suggests a novel approach to produce catalytically active Fe 2+ .…”

“…FMX enhances leukemia, breast, and lung cancer cell killing by increasing reactive oxygen species [ 20 , 21 ]. Ionizing radiation is a cancer therapy that can oxidize the Fe 3 O 4 core of FMX to enhance iron release, furthering its redox activity [ 22 ]. Here we demonstrate that AscH − catalyzes FMX decomposition to enhance H 2 O 2 -dependent GBM cell killing and tumor control in vivo .…”

Strategic design and fabrication of lightweight sesame ball-like hollow double-layer hybrid magnetic molecularly imprinted nanomaterials for the highly specific separation and recovery of tetracycline from milk

“…The recovery of TC from milk sample ranged from 94.8%–98.5%. In addition, both dopamine and Fe 3 O 4 nanoparticles have been approved by the Food and Drug Administration for the treatment of different diseases, 46,47 as they have demonstrated great potential in several biomedical and pharmaceutical applications due to their non-toxic, biocompatibility, and biodegradability. 48,49 Thus, HD-MMIPs are considered a green and non-toxic adsorbent, so any residual adsorbents would not cause any kind of biotoxicity or environmental toxicity.…”

Prospects of Nanoparticle-based Radioenhancement for Radiotherapy

“…[261] Although developed and FDA-approved for the treatment of iron deficiency anemia, Ferumoxytol (iron oxide NPs) may serve as a radiotherapy adjuvant, releasing iron during irradiation. [262] Ferumoxytol is now in clinical trials for the therapy of primary and metastatic hepatic cancers (NCT04682847). Though not developed as a radioenhancer, another iron oxide nanoparticle formulation, NanoTherm® (developed by MagForce) is FDA approved and currently in clinical trials for the focal ablation of prostate cancers using a magnetic field (Phase IIb: NCT05010759).…”