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Nanomaterial-Based Radiosensitization 3.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Physical Chemistry and Chemical Physics".

Deadline for manuscript submissions: closed (14 July 2023) | Viewed by 10651

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Dr. Ivan Kempson

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Guest Editor

Future Industries Institute, University of South Australia, Mawson Lakes, SA 5095, Australia
Interests: nanomedicine; bio-inorganic interactions; physical chemistry; nanoparticles; radiotherapy; trace-elements
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Radiotherapies are highly effective and economical. For instance, in cancer treatment, radiotherapy contributes to about 40% of cures and yet accounts for less than 10% of cancer treatment costs. The delivery of electromagnetic radiation and energetic particles has advanced tremendously due to technical, engineering, and physical accomplishments. However, many treatments now have limited scope for further improvements without advancing our basic understanding and exploitation or manipulation of the physical, chemical, and biological attributes associated with the morbidity in question.

In this regard, nanomaterials offer avenues for enhancing current therapies and the exploration of experimental therapies by preferentially sensitizing target tissues. A wave of ideas and technologies is building, with a number entering clinical trials and market approval achieved. These technologies span diverse concepts aimed at enhancing physical, chemical, and biological mechanisms, developing nanoparticles for targeted delivery, and the controlled delivery and release of radiosensitizing agents (small molecules, biologicals, and nanoparticles).

With emerging knowledge, the molecular-scale roles in radiosensitization are increasingly critical to understanding mechanisms and developing radiosensitizers to enhance the interaction of electromagnetic radiation and particle interactions with biology. This Special Issue of the International Journal of Molecular Sciences will provide an exciting insight into state-of-the-art radiosensitization with nanomaterial technologies.

Dr. Ivan Kempson
Guest Editor

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Keywords

nanomaterials
nanoparticles
radiosensitizers
external beam radiotherapy
photodynamic therapy
brachytherapy
targeted alpha/beta therapy
particle therapy

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Published Papers (5 papers)

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Research

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23 pages, 4355 KiB

Open AccessArticle

Nanodiamond Effects on Cancer Cell Radiosensitivity: The Interplay between Their Chemical/Physical Characteristics and the Irradiation Energy

by Veronica Varzi, Emiliano Fratini, Mauro Falconieri, Daniela Giovannini, Alessia Cemmi, Jessica Scifo, Ilaria Di Sarcina, Pietro Aprà, Sofia Sturari, Lorenzo Mino, Giulia Tomagra, Erminia Infusino, Valeria Landoni, Carmela Marino, Mariateresa Mancuso, Federico Picollo and Simonetta Pazzaglia

Int. J. Mol. Sci. 2023, 24(23), 16622; https://doi.org/10.3390/ijms242316622 - 22 Nov 2023

Cited by 4 | Viewed by 1821

Abstract

Nanoparticles are being increasingly studied to enhance radiation effects. Among them, nanodiamonds (NDs) are taken into great consideration due to their low toxicity, inertness, chemical stability, and the possibility of surface functionalization. The objective of this study is to explore the influence of the chemical/physical properties of NDs on cellular radiosensitivity to combined treatments with radiation beams of different energies. DAOY, a human radioresistant medulloblastoma cell line was treated with NDs—differing for surface modifications [hydrogenated (H-NDs) and oxidized (OX-NDs)], size, and concentration—and analysed for (i) ND internalization and intracellular localization, (ii) clonogenic survival after combined treatment with different radiation beam energies and (iii) DNA damage and apoptosis, to explore the nature of ND–radiation biological interactions. Results show that chemical/physical characteristics of NDs are crucial in determining cell toxicity, with hydrogenated NDs (H-NDs) decreasing either cellular viability when administered alone, or cell survival when combined with radiation, depending on ND size and concentration, while OX-NDs do not. Also, irradiation at high energy (γ-rays at 1.25 MeV), in combination with H-NDs, is more efficient in eliciting radiosensitisation when compared to irradiation at lower energy (X-rays at 250 kVp). Finally, the molecular mechanisms of ND radiosensitisation was addressed, demonstrating that cell killing is mediated by the induction of Caspase-3-dependent apoptosis that is independent to DNA damage. Identifying the optimal combination of ND characteristics and radiation energy has the potential to offer a promising therapeutic strategy for tackling radioresistant cancers using H-NDs in conjunction with high-energy radiation. Full article

(This article belongs to the Special Issue Nanomaterial-Based Radiosensitization 3.0)

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21 pages, 5274 KiB

Open AccessArticle

Evaluation of Radiosensitization and Cytokine Modulation by Differentially PEGylated Gold Nanoparticles in Glioblastoma Cells

by Bríanna N. Kerr, Daniel Duffy, Caitríona E. McInerney, Ashton Hutchinson, Inaya Dabaja, Rana Bazzi, Stéphane Roux, Kevin M. Prise and Karl T. Butterworth

Int. J. Mol. Sci. 2023, 24(12), 10032; https://doi.org/10.3390/ijms241210032 - 12 Jun 2023

Viewed by 1902

Abstract

Glioblastoma (GBM) is known as the most aggressive type of malignant brain tumour, with an extremely poor prognosis of approximately 12 months following standard-of-care treatment with surgical resection, radiotherapy (RT), and temozolomide treatment. Novel RT-drug combinations are urgently needed to improve patient outcomes. Gold nanoparticles (GNPs) have demonstrated significant preclinical potential as radiosensitizers due to their unique physicochemical properties and their ability to pass the blood–brain barrier. The modification of GNP surface coatings with poly(ethylene) glycol (PEG) confers several therapeutic advantages including immune avoidance and improved cellular localisation. This study aimed to characterise both the radiosensitizing and immunomodulatory properties of differentially PEGylated GNPs in GBM cells in vitro. Two GBM cell lines were used, U-87 MG and U-251 MG. The radiobiological response was evaluated by clonogenic assay, immunofluorescent staining of 53BP1 foci, and flow cytometry. Changes in the cytokine expression levels were quantified by cytokine arrays. PEGylation improved the radiobiological efficacy, with double-strand break induction being identified as an underlying mechanism. PEGylated GNPs also caused the greatest boost in RT immunogenicity, with radiosensitization correlating with a greater upregulation of inflammatory cytokines. These findings demonstrate the radiosensitizing and immunostimulatory potential of ID11 and ID12 as candidates for RT-drug combination in future GBM preclinical investigations. Full article

(This article belongs to the Special Issue Nanomaterial-Based Radiosensitization 3.0)

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13 pages, 5596 KiB

Open AccessArticle

Capacitive Electrode-Based Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic AD Mouse Models: The Electroceutical Targeting of Alzheimer’s Disease Feasibility Study

by Younshick Choi, Won-Seok Lee, Jaemeun Lee, Sun-Hyun Park, Sunwoung Kim, Ki-Hong Kim, Sua Park, Eun Ho Kim and Jong-Ki Kim

Int. J. Mol. Sci. 2023, 24(11), 9552; https://doi.org/10.3390/ijms24119552 - 31 May 2023

Cited by 1 | Viewed by 1679

Abstract

Iron accumulation in the brain accelerates Alzheimer’s disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ fibril structure or the Aβ plaque in a mouse model of Alzheimer’s disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe₃O₄) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7–1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer’s disease (AD) mouse model revealed the degradation of the Aβ fibril or the removal of the Aβ-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD. Full article

(This article belongs to the Special Issue Nanomaterial-Based Radiosensitization 3.0)

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13 pages, 6514 KiB

Open AccessArticle

Effects of Ultrafine Single-Nanometer Oxygen Bubbles on Radiation Sensitivity in a Tumor-Bearing Mouse Model

by Navchaa Gombodorj, Takehiko Yokobori, Nobutoshi Mutsuki, Bilguun Erkhem-Ochir, Haruka Okami, Takayuki Asao, Hiroshi Saeki, Ken Shirabe and Dai Yamanouchi

Int. J. Mol. Sci. 2022, 23(12), 6838; https://doi.org/10.3390/ijms23126838 - 20 Jun 2022

Cited by 3 | Viewed by 2410

Abstract

Radiation therapy against cancer cells often causes radiation resistance via accumulation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) under hypoxic conditions and severe side effects. Radiation sensitizers without side effects are required to overcome hypoxia-induced radiation resistance and decrease radiation-related side effects in patients with refractory cancer. We previously developed oxygen nanobubble water (NBO₂ water) and demonstrated that it suppresses hypoxia-induced radiation resistance in cancer cell lines within the single-nanometer range. This study aimed to elucidate whether NBO₂ water could act as a radiosensitizer via regulation of HIF-1α in a tumor-bearing mouse model. Six-week-old female BALB/c mice subcutaneously injected with tumor cells received control water or NBO₂ water for 28 days, after which biochemical examinations and radiation treatment were performed. Hypoxic tumor regions were detected immunohistochemically. We found that NBO₂ water sensitized radiation reactivity in the xenografted tumors. Notably, NBO₂ water administration downregulated the accumulation of HIF-1α in xenografted tumors and did not affect the vital organs of healthy mice. The combination of radiation and single-nanometer NBO₂ water without severe side effects may be a promising therapeutic option to improve radiation sensitivity in cancer patients without tolerance to invasive treatments. Full article

(This article belongs to the Special Issue Nanomaterial-Based Radiosensitization 3.0)

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Review

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19 pages, 2085 KiB

Open AccessReview

Bio-Inorganic Layered Double Hydroxide Nanohybrids in Photochemotherapy: A Mini Review

by N. Sanoj Rejinold, Goeun Choi and Jin-Ho Choy

Int. J. Mol. Sci. 2022, 23(19), 11862; https://doi.org/10.3390/ijms231911862 - 6 Oct 2022

Cited by 3 | Viewed by 2130

Abstract

Clay-based bio-inorganic nanohybrids, such as layered double hydroxides (LDH), have been extensively researched in the various fields of biomedicine, particularly for drug delivery and bio-imaging applications. Recent trends indicate that such two-dimensional LDH can be hybridized with a variety of photo-active biomolecules to selectively achieve anti-cancer benefits through numerous photo/chemotherapies (PCT), including photothermal therapy, photodynamic therapy, and magnetic hyperthermia, a combination of therapies to achieve the best treatment regimen for patients that cannot be treated either by surgery or radiation alone. Among the novel two-dimensional clay-based bio-inorganic nanohybrids, LDH could enhance the photo-stability and drug release controllability of the PCT agents, which would, in turn, improve the overall phototherapeutic performance. This review article highlights the most recent advances in LDH-based two-dimensional clay-bio-inorganic nanohybrids for the aforementioned applications. Full article

(This article belongs to the Special Issue Nanomaterial-Based Radiosensitization 3.0)

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