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

Petronek, Michael; Teferi, N.; Caster, Joseph M.; Stolwijk, Jeffrey M.; Zaher, Amira; Buatti, John M.; Hasan, David; Wafa, Emad I.; Salem, Aliasger K.; Gillan, Edward G.; Aubin, J.J. St –; Buettner, Garry R.; Spitz, Douglas R.; Magnotta, Vincent; Allen, Bryan G.

doi:10.1016/j.redox.2023.102651

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…The metabolic activity and proliferation rate of tumor cells are typically elevated compared to their healthy counterparts, resulting in a markedly increased demand for iron. This observation underscores the critical role of iron in the development and progression of tumors, and also in GBM [69]. The expression levels of iron-regulated genes (for example, TfR1 and TfR2) are regulated in a different manner between neoplastic brain tissues and normal human brain tissue, with either upregulation or downregulation being observed [70].…”

Section: The Crucial Role Of Glial Cellsmentioning

confidence: 72%

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Onciul,

Brehar,

Toader

et al. 2024

CIMB

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Gliomas constitute a diverse and complex array of tumors within the central nervous system (CNS), characterized by a wide range of prognostic outcomes and responses to therapeutic interventions. This literature review endeavors to conduct a thorough investigation of gliomas, with a particular emphasis on glioblastoma (GBM), beginning with their classification and epidemiological characteristics, evaluating their relative importance within the CNS tumor spectrum. We examine the immunological context of gliomas, unveiling the intricate immune environment and its ramifications for disease progression and therapeutic strategies. Moreover, we accentuate critical developments in understanding tumor behavior, focusing on recent research breakthroughs in treatment responses and the elucidation of cellular signaling pathways. Analyzing the most novel transcriptomic studies, we investigate the variations in gene expression patterns in glioma cells, assessing the prognostic and therapeutic implications of these genetic alterations. Furthermore, the role of epigenetic modifications in the pathogenesis of gliomas is underscored, suggesting that such changes are fundamental to tumor evolution and possible therapeutic advancements. In the end, this comparative oncological analysis situates GBM within the wider context of neoplasms, delineating both distinct and shared characteristics with other types of tumors.

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Section: The Crucial Role Of Glial Cellsmentioning

confidence: 72%

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Onciul,

Brehar,

Toader

et al. 2024

CIMB

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“…Moreover, it has recently been reported that the combination of FMX and AscH − exhibited enhanced cytotoxic effects in glioblastoma cells and significantly enhanced the standard of care therapy (radiation and temozolomide) in an in vivo animal model [ 19 ]. Thus, the therapeutic aspect of these imaging results was subsequently evaluated in glioblastoma cells.…”

Section: Resultsmentioning

confidence: 99%

“…AscH − can reduce and release Fe 2+ from ferritin, a Fe 3+ -containing biological macromolecule that is the primary mechanism for intracellular iron storage [ 16 , 17 , 18 ]. Recently, it has been reported that AscH − catalyzes the decomposition of the FMX Fe 3 O 4 core [ 19 ]. The chemical interaction between FMX and AscH − can be characterized by a significant reduction in FMX size (≈66% reduction in 24 h), a release of redox-active Fe 2+ that follows Michaelis–Menton kinetics, and a significant increase in H 2 O 2 generation.…”

Section: Introductionmentioning

confidence: 99%

“…The chemical interaction between FMX and AscH − can be characterized by a significant reduction in FMX size (≈66% reduction in 24 h), a release of redox-active Fe 2+ that follows Michaelis–Menton kinetics, and a significant increase in H 2 O 2 generation. The decomposition of FMX by AscH − was reported to enhance glioblastoma cell killing and importantly, the enhanced toxicity of FMX and AscH − was glioblastoma specific, as no significant in vitro toxicity was observed in normal human astrocytes [ 19 ]. Thus, the chemical pairing of FMX and AscH − represents a novel therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

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MRI Detection and Therapeutic Enhancement of Ferumoxytol Internalization in Glioblastoma Cells

Petronek,

Teferi,

Lee

et al. 2024

Nanomaterials

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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.

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“…[65,66] They can be induced by exogenous stimuli-responsiveness, endogenous stimuli-responsiveness, or a combination of both. [67][68][69] By subtly changing the TME and external factors, stimuli-responsive nanomaterials are able to increase radio-sensitization through mechanisms such as size/shape transformation, structural degradation, and controllable drug release. [70][71][72] These mechanisms enhance tumor accumulation/penetration and prolong blood circulation time, thereby further sensitizing radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

Xiao,

Zhao,

Sun

et al. 2023

Small Methods

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Radiotherapy (RT) has been a classical therapeutic method of cancer for several decades. It attracts tremendous attention for the precise and efficient treatment of local tumors with stimuli‐responsive nanomaterials, which enhance RT. However, there are few systematic reviews summarizing the newly emerging stimuli‐responsive mechanisms and strategies used for tumor radio‐sensitization. Hence, this review provides a comprehensive overview of recently reported studies on stimuli‐responsive nanomaterials for radio‐sensitization. It includes four different approaches for sensitized RT, namely endogenous response, exogenous response, dual stimuli‐response, and multi stimuli‐response. Endogenous response involves various stimuli such as pH, hypoxia, GSH, and reactive oxygen species (ROS), and enzymes. On the other hand, exogenous response encompasses X‐ray, light, and ultrasound. Dual stimuli‐response combines pH/enzyme, pH/ultrasound, and ROS/light. Lastly, multi stimuli‐response involves the combination of pH/ROS/GSH and X‐ray/ROS/GSH. By elaborating on these responsive mechanisms and applying them to clinical RT diagnosis and treatment, these methods can enhance radiosensitive efficiency and minimize damage to surrounding normal tissues. Finally, this review discusses the additional challenges and perspectives related to stimuli‐responsive nanomaterials for tumor radio‐sensitization.

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

Cited by 11 publications

References 34 publications

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

Deciphering Glioblastoma: Fundamental and Novel Insights into the Biology and Therapeutic Strategies of Gliomas

MRI Detection and Therapeutic Enhancement of Ferumoxytol Internalization in Glioblastoma Cells

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

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