Ion Beam Stimulation Therapy With a Nanoradiator as a Site-Specific Prodrug

Kim, Jongki; Seo, Sang Woo; Jeon, Jae-Geun

doi:10.3389/fphy.2020.00270

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…The irradiated mice were returned to the animal housing room of the heavy ion facility and kept in individual cages for 3-10 days. The whole brain was irradiated via carbon beam transmission with a pristine Bragg peak behind the head (20)(21)(22)(23) as shown in Fig. 1.…”

Section: Cis Treatmentmentioning

confidence: 99%

Carbon beam transmission therapy reverses iron deposits and microglia-driven neuroinflammation and induces cognitive improvement in an Alzheimer’s disease mouse model.

Lee,

Choi,

Kokubo

et al. 2024

Preprint

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Background Insoluble iron deposits often exist as iron oxide nanoparticles in protein aggregates, impaired ferritin, or activated microglia, and have been implicated as a major culprit of neuroinflammation in Alzheimer’s disease. However, no crucial evidence has been reported to support the therapeutic effects of current iron chelators on the deposition of various molecular forms of insoluble iron. Methods We investigated the therapeutic effect of carbon ion stimulation (CIS) via the use of a transmission beam on insoluble iron deposits and the associated biological response in AD mouse brains. Results Compared no treatment, CIS dose-dependently induced a 33–60% reduction in the amount of ferrous-containing iron species and associated inclusion bodies in the brains of AD mice. CIS induced considerable neuroinflammation downregulation and conversely anti-inflammatory upregulation, which was associated with improved memory and enhanced hippocampal neurogenesis. Conclusions In conclusion, our results suggest that the effective degradation of insoluble iron deposits in combination with pathogenic inclusion bodies plays a role in promoting AD-modifying properties and offers a potential carbon ion treatment option for AD.

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Section: Cis Treatmentmentioning

confidence: 99%

Carbon beam transmission therapy reverses iron deposits and microglia-driven neuroinflammation and induces cognitive improvement in an Alzheimer’s disease mouse model.

Lee,

Choi,

Kokubo

et al. 2024

Preprint

Self Cite

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“…Although a number of reviews regarding this topic have been published, the reviews have focused almost exclusively on photon irradiation (e.g., low-energy (keV) and high-energy (MeV) photons) [ 24 , 25 , 26 ]. In fact, since the physical mechanism is different from photon RT and particle therapy [ 27 , 28 ], there has been an increasing number of studies focused on the potential of particle therapy combined with specific NREs, particularly involving gadolinium, and hafnium. Therefore, this topical review is motivated by recent developments using NREs to enhance particle therapy in preclinical and clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Metal-Based NanoEnhancers for Particle Therapy

Chuang

Shen

et al. 2023

Nanomaterials

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Radiotherapy is one of the most common therapeutic regimens for cancer treatment. Over the past decade, proton therapy (PT) has emerged as an advanced type of radiotherapy (RT) that uses proton beams instead of conventional photon RT. Both PT and carbon-ion beam therapy (CIBT) exhibit excellent therapeutic results because of the physical characteristics of the resulting Bragg peaks, which has been exploited for cancer treatment in medical centers worldwide. Although particle therapies show significant advantages to photon RT by minimizing the radiation damage to normal tissue after the tumors, they still cause damage to normal tissue before the tumor. Since the physical mechanisms are different from particle therapy and photon RT, efforts have been made to ameliorate these effects by combining nanomaterials and particle therapies to improve tumor targeting by concentrating the radiation effects. Metallic nanoparticles (MNPs) exhibit many unique properties, such as strong X-ray absorption cross-sections and catalytic activity, and they are considered nano-radioenhancers (NREs) for RT. In this review, we systematically summarize the putative mechanisms involved in NRE-induced radioenhancement in particle therapy and the experimental results in in vitro and in vivo models. We also discuss the potential of translating preclinical metal-based NP-enhanced particle therapy studies into clinical practice using examples of several metal-based NREs, such as SPION, Abraxane, AGuIX, and NBTXR3. Furthermore, the future challenges and development of NREs for PT are presented for clinical translation. Finally, we propose a roadmap to pursue future studies to strengthen the interplay of particle therapy and nanomedicine.

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Proton Stimulation Targeting Plaque Magnetite Reduces Amyloid-β Plaque and Iron Redox Toxicity and Improves Memory in an Alzheimer’s Disease Mouse Model

Seo

Chang

Jeon

et al. 2021

JAD

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Background: The coexistence of magnetite within protein aggregates in the brain is a typical pathologic feature of Alzheimer’s disease (AD), and the formation of amyloid-β (Aβ) plaques induces critical impairment of cognitive function. Objective: This study aimed to investigate the therapeutic effect of proton stimulation (PS) targeting plaque magnetite in the transgenic AD mouse brain. Methods: A proton transmission beam was applied to the whole mouse brain at a single entrance dose of 2 or 4 Gy to test the effect of disruption of magnetite-containing Aβ plaques by electron emission from magnetite. The reduction in Aβ plaque burden and the cognitive function of the PS-treated mouse group were assayed by histochemical analysis and memory tests, respectively. Aβ-magnetite and Aβ fibrils were treated with PS to investigate the breakdown of the amyloid protein matrix. Results: Single PS induced a 48–87%reduction in both the amyloid plaque burden and ferrous-containing magnetite level in the early-onset AD mouse brain while saving normal tissue. The overall Aβ plaque burden (68–82%) and (94–97%) hippocampal magnetite levels were reduced in late onset AD mice that showed improvements in cognitive function after PS compared with untreated AD mice (p < 0.001). Analysis of amyloid fibrils after exposure to a single 2 or 4 Gy proton transmission beam demonstrated that the protein matrix was broken down only in magnetite-associated Aβ fibrils. Conclusion: Single PS targeting plaque magnetite effectively decreases the amyloid plaque burden and the ferrous-containing magnetite level, and this effect is useful for memory recovery.

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Ion Beam Stimulation Therapy With a Nanoradiator as a Site-Specific Prodrug

Cited by 3 publications

References 27 publications

Carbon beam transmission therapy reverses iron deposits and microglia-driven neuroinflammation and induces cognitive improvement in an Alzheimer’s disease mouse model.

Carbon beam transmission therapy reverses iron deposits and microglia-driven neuroinflammation and induces cognitive improvement in an Alzheimer’s disease mouse model.

Recent Advances in Metal-Based NanoEnhancers for Particle Therapy

Proton Stimulation Targeting Plaque Magnetite Reduces Amyloid-β Plaque and Iron Redox Toxicity and Improves Memory in an Alzheimer’s Disease Mouse Model

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