Journal article
MRI Detection and Therapeutic Enhancement of Ferumoxytol Internalization in Glioblastoma Cells
Nanomaterials (Basel, Switzerland), Vol.14(2), 189
01/13/2024
DOI: 10.3390/nano14020189
PMCID: PMC10821426
PMID: 38251153
Abstract
Recently, the FDA-approved iron oxide nanoparticle, ferumoxytol, has been found to enhance the efficacy of pharmacological ascorbate (AscH−) in treating glioblastoma, as AscH− reduces the Fe3+ sites in the nanoparticle core. Given the iron oxidation state specificity of T2* relaxation mapping, this study aims to investigate the ability of T2* relaxation to monitor the reduction of ferumoxytol by AscH− with respect to its in vitro therapeutic enhancement. This study employed an in vitro glioblastoma MRI model system to investigate the chemical interaction of ferumoxytol with T2* mapping. Lipofectamine was utilized to facilitate ferumoxytol internalization and assess intracellular versus extracellular chemistry. In vitro T2* mapping successfully detected an AscH−-mediated reduction of ferumoxytol (25.6 ms versus 2.8 ms for FMX alone). The T2* relaxation technique identified the release of Fe2+ from ferumoxytol by AscH− in glioblastoma cells. However, the high iron content of ferumoxytol limited T2* ability to differentiate between the external and internal reduction of ferumoxytol by AscH− (ΔT2* = +839% for external FMX and +1112% for internal FMX reduction). Notably, the internalization of ferumoxytol significantly enhances its ability to promote AscH− toxicity (dose enhancement ratio for extracellular FMX = 1.16 versus 1.54 for intracellular FMX). These data provide valuable insights into the MR-based nanotheranostic application of ferumoxytol and AscH− therapy for glioblastoma management. Future developmental efforts, such as FMX surface modifications, may be warranted to enhance this approach further.
Details
- Title: Subtitle
- MRI Detection and Therapeutic Enhancement of Ferumoxytol Internalization in Glioblastoma Cells
- Creators
- Michael S. Petronek - University of IowaNahom Teferi - University of Iowa Hospitals and ClinicsChu-Yu Lee - University of Iowa, RadiologyVincent A Magnotta - University of Iowa, Iowa Neuroscience InstituteBryan G Allen - University of Iowa, Radiation Oncology
- Resource Type
- Journal article
- Publication Details
- Nanomaterials (Basel, Switzerland), Vol.14(2), 189
- DOI
- 10.3390/nano14020189
- PMID
- 38251153
- PMCID
- PMC10821426
- NLM abbreviation
- Nanomaterials (Basel)
- ISSN
- 2079-4991
- eISSN
- 2079-4991
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: P01 CA217797, R21CA270742, P30 CA086862; DOI: 10.13039/100001634, name: Gateway for Cancer Research, award: G-17-1500; name: Carver College of Medicine; name: Holden Comprehensive Cancer Center
- Language
- English
- Date published
- 01/13/2024
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Psychiatry; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984548410302771
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