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

M S Petronek; N Teferi; J M Caster; J M Stolwijk; A Zaher; J M Buatti; D Hasan; E I Wafa; A K Salem; E G Gillan; J J St-Aubin; G R Buettner; D R Spitz; V A Magnotta; B G Allen

doi:10.1016/j.redox.2023.102651

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

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

M S Petronek, N Teferi, J M Caster, J M Stolwijk, A Zaher, J M Buatti, D Hasan, E I Wafa, A K Salem, E G Gillan, …

Redox biology, Vol.62, 102651

03/07/2023

DOI: 10.1016/j.redox.2023.102651

PMCID: PMC10025281

PMID: 36924683

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Abstract

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.

Details

Title: Subtitle: Magnetite nanoparticles as a kinetically favorable source of iron to enhance GBM response to chemoradiosensitization with pharmacological ascorbate
Creators: M S Petronek - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA. Electronic address: Michael-petronek@uiowa.edu
N Teferi - Department of Neurosurgery, University of Iowa, Iowa City, IA, USA
J M Caster - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA
J M Stolwijk - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA
A Zaher - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA
J M Buatti - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA
D Hasan - Duke University
E I Wafa - Department of Pharmaceutical Sciences, University of Iowa, Iowa City, IA, USA
A K Salem - Department of Pharmaceutical Sciences, University of Iowa, Iowa City, IA, USA
E G Gillan - Department of Chemistry, University of Iowa, Iowa City, IA, USA
J J St-Aubin - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA
G R Buettner - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA
D R Spitz - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA
V A Magnotta - Department of Radiology, University of Iowa, Iowa City, IA, USA
B G Allen - Department of Radiation Oncology, University of Iowa, Iowa City, IA, USA. Electronic address: bryan-allen@uiowa.edu
Resource Type: Journal article
Publication Details: Redox biology, Vol.62, 102651
DOI: 10.1016/j.redox.2023.102651
PMID: 36924683
PMCID: PMC10025281
NLM abbreviation: Redox Biol
ISSN: 2213-2317
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: P01 CA217797, P01 CA244091, R21 CA256301, T32 CA078586; DOI: 10.13039/100000009, name: Foundation for the National Institutes of Health; DOI: 10.13039/100001634, name: Gateway for Cancer Research, award: G-17-1500; DOI: 10.13039/100015515, name: Roy J. and Lucille A. Carver College of Medicine, University of Iowa, award: P30 CA086862
Language: English
Date published: 03/07/2023
Academic Unit: Psychiatry; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Radiation Research Laboratory; Chemical and Biochemical Engineering; Otolaryngology; Roy J. Carver Department of Biomedical Engineering; Radiology; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Chemistry; Dental Research; Neurosurgery; Internal Medicine
Record Identifier: 9984378329902771

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