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BNCT Drug Development and Preclinical Testing
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BNCT Drug Development and Preclinical Testing

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 9906

Special Issue Editors

Prof. Dr. Wolfgang Sauerwein

E-Mail Website
Guest Editor
1. Radiation Oncology, University Hospital Essen, University Duisburg, Strahlenklinik, Hufeland Street 55, 45122 Essen, Germany
2. Neutron Therapy Research Center, Okayama University, Okayama 700-8530, Japan
3. German Society for Boron Neutron Capture Therapy, 45122 Essen, Germany
Interests: radiation oncology; hadron therapy; boron neutron capture therapy (BNCT); neutrons; high-LET radiation; radiation biology; eye tumors; ophthalmic oncology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Lucie Sancey

E-Mail Website1 Website2
Guest Editor
Institute for Advanced Biosciences INSERM U1209, CNRS UMR5309 UGA, Allée des Alpes-Site Santé, 38700 La Tronche, France
Interests: cancer biology; imaging; BNCT; elemental imaging; activable X-ray nanodrugs; theranostic compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Sunil Krishnan

E-Mail Website
Guest Editor
Mayo Clinic Florida, Jacksonville, FL 32224, USA
Interests: radiation oncology; gastrointestinal cancer; nanotechnology

Special Issue Information

Dear Colleagues,

The appearance of hospital-based epithermal neutron sources has made boron neutron capture therapy (BNCT) a dedicated focus of innovative developments in radiation oncology. This binary treatment modality not only needs neutrons but also a carrier transporting B-10 selectively into cancer cells. This has fueled the quest for new compounds for BNCT and resurgence of interest in preclinical testing of these next-generation compounds.

This Special Issue of Cells is dedicated to collating results of recent preclinical research related to the development and testing of novel boron-containing therapeutic compounds and publishing a collection of intelligible and clear reviews of the most challenging aspects of drug development for BNCT. You are invited to submit your contributions in the form of original research articles, reviews, or shorter perspective articles.

Prof. Dr. Wolfgang Sauerwein
Prof. Dr. Lucie Sancey
Dr. Sunil Krishnan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Boron Neutron Capture Therapy
  • BNCT
  • boron-10
  • drug development
  • targeted therapy
  • vectorized therapy
  • radiation oncology

Related Special Issues

Published Papers (5 papers)

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Research

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18 pages, 3669 KiB  
Article
Proteomic Characterization of SAS Cell-Derived Extracellular Vesicles in Relation to Both BPA and Neutron Irradiation Doses
by Davide Perico, Ying Tong, Lichao Chen, Shoji Imamichi, Yu Sanada, Masamichi Ishiai, Minoru Suzuki, Mitsuko Masutani and Pierluigi Mauri
Cells 2023, 12(12), 1562; https://doi.org/10.3390/cells12121562 - 06 Jun 2023
Cited by 1 | Viewed by 1712
Abstract
Boron neutron capture therapy (BNCT) is a selective radiotherapy based on nuclear reaction that occurs when 10B atoms accumulated in cancer cells are irradiated by thermal neutrons, triggering a nuclear fission response leading to cell death. Despite its growing importance in cancer [...] Read more.
Boron neutron capture therapy (BNCT) is a selective radiotherapy based on nuclear reaction that occurs when 10B atoms accumulated in cancer cells are irradiated by thermal neutrons, triggering a nuclear fission response leading to cell death. Despite its growing importance in cancer treatment, molecular characterization of its effects is still lacking. In this context, proteomics investigation can be useful to study BNCT effect and identify potential biomarkers. Hence, we performed proteomic analysis with nanoLC-MS/MS (liquid chromatography coupled to tandem mass spectrometry) on extracellular vesicles (EVs) isolated from SAS cultures treated or not with 10B-boronophenylalanine (BPA) and different doses of neutron irradiation, to study the cellular response related to both boron administration and neutrons action. Despite the interference of fetal bovine serum in the medium, we were able to stratify BPA− and BPA+ conditions and to identify EVs-derived proteins characterizing pathways potentially related to a BNCT effect such as apoptosis, DNA repair and inflammatory response. In particular, KLF11, SERPINA1 and SERPINF2 were up-regulated in BPA+, while POLE and SERPINC1 were up-regulated in BPA−. These results provide the first proteomic investigation of EVs treated with BNCT in different conditions and highlight the potentiality of proteomics for improving biomarkers identification and mechanisms understanding of BNCT. Full article
(This article belongs to the Special Issue BNCT Drug Development and Preclinical Testing)
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12 pages, 1334 KiB  
Article
Enhancement in the Therapeutic Efficacy of In Vivo BNCT Mediated by GB-10 with Electroporation in a Model of Oral Cancer
by Nahuel Olaiz, Andrea Monti Hughes, Emiliano C. C. Pozzi, Silvia Thorp, Paula Curotto, Verónica A. Trivillin, Paula S. Ramos, Mónica A. Palmieri, Guillermo Marshall, Amanda E. Schwint and Marcela A. Garabalino
Cells 2023, 12(9), 1241; https://doi.org/10.3390/cells12091241 - 25 Apr 2023
Cited by 2 | Viewed by 1193
Abstract
Boron neutron capture therapy (BNCT) combines preferential tumor uptake of 10B compounds and neutron irradiation. Electroporation induces an increase in the permeability of the cell membrane. We previously demonstrated the optimization of boron biodistribution and microdistribution employing electroporation (EP) and decahydrodecaborate (GB-10) [...] Read more.
Boron neutron capture therapy (BNCT) combines preferential tumor uptake of 10B compounds and neutron irradiation. Electroporation induces an increase in the permeability of the cell membrane. We previously demonstrated the optimization of boron biodistribution and microdistribution employing electroporation (EP) and decahydrodecaborate (GB-10) as the boron carrier in a hamster cheek pouch oral cancer model. The aim of the present study was to evaluate if EP could improve tumor control without enhancing the radiotoxicity of BNCT in vivo mediated by GB-10 with EP 10 min after GB-10 administration. Following cancerization, tumor-bearing hamster cheek pouches were treated with GB-10/BNCT or GB-10/BNCT + EP. Irradiations were carried out at the RA-3 Reactor. The tumor response and degree of mucositis in precancerous tissue surrounding tumors were evaluated for one month post-BNCT. The overall tumor response (partial remission (PR) + complete remission (CR)) increased significantly for protocol GB-10/BNCT + EP (92%) vs. GB-10/BNCT (48%). A statistically significant increase in the CR was observed for protocol GB-10/BNCT + EP (46%) vs. GB-10/BNCT (6%). For both protocols, the radiotoxicity (mucositis) was reversible and slight/moderate. Based on these results, we concluded that electroporation improved the therapeutic efficacy of GB-10/BNCT in vivo in the hamster cheek pouch oral cancer model without increasing the radiotoxicity. Full article
(This article belongs to the Special Issue BNCT Drug Development and Preclinical Testing)
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20 pages, 3787 KiB  
Article
Novel Self-Forming Nanosized DDS Particles for BNCT: Utilizing A Hydrophobic Boron Cluster and Its Molecular Glue Effect
by Abdul Basith Fithroni, Kazuko Kobayashi, Hirotaka Uji, Manabu Ishimoto, Masaru Akehi, Takashi Ohtsuki and Eiji Matsuura
Cells 2022, 11(20), 3307; https://doi.org/10.3390/cells11203307 - 21 Oct 2022
Cited by 3 | Viewed by 2719
Abstract
BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we [...] Read more.
BNCT is a non-invasive cancer therapy that allows for cancer cell death without harming adjacent cells. However, the application is limited, owing to the challenges of working with clinically approved boron (B) compounds and drug delivery systems (DDS). To address the issues, we developed self-forming nanoparticles consisting of a biodegradable polymer, namely, “AB-type Lactosome (AB-Lac)” loaded with B compounds. Three carborane isomers (o-, m-, and p-carborane) and three related alkylated derivatives, i.e., 1,2-dimethy-o-carborane (diC1-Carb), 1,2-dihexyl-o-carborane (diC6-Carb), and 1,2-didodecyl-o-carborane (diC12-Carb), were separately loaded. diC6-Carb was highly loaded with AB-Lac particles, and their stability indicated the “molecular glue” effect. The efficiency of in vitro B uptake of diC6-Carb for BNCT was confirmed at non-cytotoxic concentration in several cancer cell lines. In vivo/ex vivo biodistribution studies indicated that the AB-Lac particles were remarkably accumulated within 72 h post-injection in the tumor lesions of mice bearing syngeneic breast cancer (4T1) cells, but the maximum accumulation was reached at 12 h. In ex vivo B biodistribution, the ratios of tumor/normal tissue (T/N) and tumor/blood (T/Bl) of the diC6-Carb-loaded particles remained stably high up to 72 h. Therefore, we propose the diC6-Carb-loaded AB-Lac particles as a promising candidate medicine for BNCT. Full article
(This article belongs to the Special Issue BNCT Drug Development and Preclinical Testing)
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11 pages, 1442 KiB  
Article
Evaluation of the Key Advantages between Two Modalities of Boronophenylalanine Administration for Clinical Boron Neutron Capture Therapy Using an Animal Model
by Yu-Chuan Lin, Yi-Jang Lee, Yi-Wei Chen, Shan-Ying Wang and Fong-In Chou
Cells 2022, 11(17), 2736; https://doi.org/10.3390/cells11172736 - 01 Sep 2022
Cited by 2 | Viewed by 1450
Abstract
In clinical boron neutron capture therapy (BNCT), boronophenylalanine (BPA) administrations through one-step infusion (OSI) and two-step infusion (TSI) are the most widely used. This study compared the advantages of OSI and TSI using a human oral squamous cell carcinoma-bearing animal model. OSI was [...] Read more.
In clinical boron neutron capture therapy (BNCT), boronophenylalanine (BPA) administrations through one-step infusion (OSI) and two-step infusion (TSI) are the most widely used. This study compared the advantages of OSI and TSI using a human oral squamous cell carcinoma-bearing animal model. OSI was administered at a high-dose rate of 20 mg/kg/min for 20 min (total dose: 400 mg/kg) as the first step infusion. TSI was a prolonged infusion at a low-dose rate of 1.67 mg/kg/min for 15, 30, 45, and 60 min (total dose: 25, 50, 75, and 100 mg/kg) following the first step infusion. The sigmoid Emax model was used to evaluate the boron accumulation effect in the tumor. The advantages of TSI were observed to be greater than those of OSI. The observed advantages of TSI were as follows: a stable level of boron concentration in blood; tumor to blood boron ratio (T/B); tumor to muscle boron ratio (T/M); and skin to blood boron ratio (S/B). The boron accumulation effect in tumors increased to 68.98%. Thus, effective boron concentration in these tumor cells was achieved to enhance the lethal damage in BNCT treatment. Boron concentration in the blood was equal to that in the skin. Therefore, the equivalent dose was accurately estimated for the skin. Full article
(This article belongs to the Special Issue BNCT Drug Development and Preclinical Testing)
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Review

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19 pages, 1849 KiB  
Review
Next-Generation Boron Drugs and Rational Translational Studies Driving the Revival of BNCT
by Danushka S. Seneviratne, Omran Saifi, Yuri Mackeyev, Timothy Malouff and Sunil Krishnan
Cells 2023, 12(10), 1398; https://doi.org/10.3390/cells12101398 - 16 May 2023
Cited by 6 | Viewed by 1941
Abstract
BNCT is a high-linear-energy transfer therapy that facilitates tumor-directed radiation delivery while largely sparing adjacent normal tissues through the biological targeting of boron compounds to tumor cells. Tumor-specific accumulation of boron with limited accretion in normal cells is the crux of successful BNCT [...] Read more.
BNCT is a high-linear-energy transfer therapy that facilitates tumor-directed radiation delivery while largely sparing adjacent normal tissues through the biological targeting of boron compounds to tumor cells. Tumor-specific accumulation of boron with limited accretion in normal cells is the crux of successful BNCT delivery. Given this, developing novel boronated compounds with high selectivity, ease of delivery, and large boron payloads remains an area of active investigation. Furthermore, there is growing interest in exploring the immunogenic potential of BNCT. In this review, we discuss the basic radiobiological and physical aspects of BNCT, traditional and next-generation boron compounds, as well as translational studies exploring the clinical applicability of BNCT. Additionally, we delve into the immunomodulatory potential of BNCT in the era of novel boron agents and examine innovative avenues for exploiting the immunogenicity of BNCT to improve outcomes in difficult-to-treat malignancies. Full article
(This article belongs to the Special Issue BNCT Drug Development and Preclinical Testing)
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