Ferumoxytol (FMX) is an FDA-approved magnetite (Fe₃O₄) nanoparticle used to treat iron deficiency anemia that can also be used as an MR imaging agent in patients that can't receive gadolinium. Pharmacological ascorbate (P-AscH-; IV delivery; plasma levels ≈ 20 mM) has shown promise as an adjuvant to standard of care chemo-radiotherapy in glioblastoma (GBM). Since ascorbate toxicity mediated by H₂O₂ is enhanced by Fe redox cycling, the current study determined if ascorbate catalyzed the release of ferrous iron (Fe²⁺) from FMX for enhancing GBM responses to chemo-radiotherapy. Ascorbate interacted with Fe₃O₄ in FMX to produce redox-active Fe²⁺ while simultaneously generating increased H₂O₂ fluxes, that selectively enhanced GBM cell killing (relative to normal human astrocytes) as opposed to a more catalytically active Fe complex (EDTA-Fe³⁺) in an H₂O₂ - dependent manner. In vivo, FMX was able to improve GBM xenograft tumor control when combined with pharmacological ascorbate and chemoradiation in U251 tumors that were unresponsive to pharmacological ascorbate therapy. These data support the hypothesis that FMX combined with P-AscH- represents a novel combined modality therapeutic approach to enhance cancer cell selective chemoradiosentization in the management of glioblastoma.

Background: Fragmentation of the tunica media is a hallmark of intracranial aneurysm formation, often leading to aneurysmal progression and subsequent rupture. The objective of this study is to determine the plasma level of elastin fragments in the lumen of ruptured versus unruptured human intracranial aneurysms. Methods and Results: One hundred consecutive patients with/without ruptured saccular intracranial aneurysms undergoing endovascular coiling or stent‐assisted coiling were recruited. Blood samples were collected from the lumen of intracranial aneurysm using a microcatheter. The tip of the microcatheter was placed inside the aneurysm's sac in close proximity to the inner wall of the dome. Plasma levels of elastin fragments were measured using an ELISA ‐based method. Mean plasma level of soluble human elastin fragments was significantly greater in ruptured aneurysms when compared with nonruptured aneurysms (102.0±15.5 versus 39.3±9.6 ng/mL; P <0.001). Mean plasma level of soluble human elastin fragments did not have significant correlation with age, sex, size, or aneurysm location. Conclusions: The present study revealed that a significantly higher concentration of soluble human elastin fragments in the lumen of ruptured intracranial aneurysms when compared with nonruptured ones.