MRI Detection and Therapeutic Enhancement of Ferumoxytol Internalization in Glioblastoma Cells

Author:

Petronek Michael S.1,Teferi Nahom2ORCID,Lee Chu-Yu3,Magnotta Vincent A.3ORCID,Allen Bryan G.1

Affiliation:

1. Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA

2. Department of Neurosurgery, University of Iowa, Iowa City, IA 52242, USA

3. Department of Radiology, University of Iowa, Iowa City, IA 52242, USA

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.

Funder

NIH

Gateway for Cancer Research

Carver College of Medicine

Holden Comprehensive Cancer Center

Publisher

MDPI AG

Subject

General Materials Science,General Chemical Engineering

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