2021 Fiscal Year Research-status Report
Development of novel tumor-targeting nanoparticles for malignant brain tumor neutron capture therapy and diagnosis
| Project/Area Number |
20K07672
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ザボロノク アレクサンドル 筑波大学, 医学医療系, 助教 (20723117)
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| Co-Investigator(Kenkyū-buntansha) |
中井 啓 筑波大学, 医学医療系, 准教授 (50436284)
鶴淵 隆夫 筑波大学, 医学医療系, 講師 (70778901)
MATHIS BRYAN 筑波大学, 附属病院, 病院講師 (80794635)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | BNCT / glioma / nanoparticles / tumor targeting |
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| Outline of Annual Research Achievements |
In the 2021 fiscal year under pandemic conditions, we finalized the experimental results and prepared several publications. We analyzed the size distribution of the obtained nanoparticles and evaluated the stability of colloidal solutions before and after polymer stabilization, determining the optimal concentration of hydroxyethylcellulose at 0.1-0.3%. This ratio allows to significantly reduce the toxicity of nanoparticles and store their solution for several months without aggregation. The short- and long-term toxicity was determined by the MTS and colony-forming methods. Neutron irradiation experiments were performed at the clinical accelerator prototype close to real treatment conditions. The results of irradiation experiments with tumor cells showed the effectiveness of nanoparticles as a prospective novel compound for BNCT and their advantages over the previously used BPA. The most significant tumor cell-killing results were obtained using glioma T98 and U251 cells. These cells may be candidates for use in animal tumor models in further in vivo experiments. Based on the results of additional neutron irradiation experiments, the methodology for calculating boron dose based on gold activation was also refined. As one of the promising options, liposomal delivery of the components was actively studied to better match boron and gold in a single compound.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
We report a delay in the research progress during the pandemic due to the limited access to research facilities inside and outside the campus and the inability to travel to irradiation and other distant facilities. The problem of the elemental analysis of boron included in the polymer complex was partly solved for the stock solutions of the particles; however, the analysis of the samples can be completed only in the forthcoming fiscal year. The assembly of the boron-gold complex and ApoB-29 lipoprotein synthesis essential for the targeted delivery of the particles were initiated; however, to succeed in the synthesis, specific equipment was needed, which was inaccessible, which moves this part of the research to the forthcoming fiscal year. Animal experimental plans were submitted and approved by the university’s ethical committee; however, animal experiments were also delayed due to the inability to finalize the complex.
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| Strategy for Future Research Activity |
Future plans include further development of the ApoB-29-based targeting delivery system for nanoparticles, refining the boron-gold complex assembly using several means, including liposomes with the alternative substrate. Preparation and implementation of animal experiments using mice and rats for tumor models are also scheduled according to the initial plan. In vivo toxicity analysis, imaging, and model animal tumor treatment using nanoparticles and neutron irradiation are also planned.
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| Causes of Carryover |
Travel expenses were not utilized in 2021 due to the pandemic-related inability to travel. The obtained results were presented at the conferences online. We agreed to move the unused amount to the next fiscal year.
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| Remarks |
[受賞]
Alexander Zaboronok. In situ absorbed dose evaluation using gold nanoparticles in boron neutron capture therapy for malignant brain tumors. 第35回日本脳神経外科国際学会フォーラム, 2021年11月12日, Osaka, Japan. 第3位.
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Research Products
(7 results)
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[Journal Article] Gold Nanoparticles Permit In Situ Absorbed Dose Evaluation in Boron Neutron Capture Therapy for Malignant Tumors2021
Author(s)
Zaboronok A., Taskaev S., Volkova O., Mechetina L., Kasatova A., Sycheva T., Nakai K., Kasatov D., Makarov A., Kolesnikov I., Shchudlo I., Bykov T., Sokolova E., Koshkarev A., Kanygin V., Kichigin A., Mathis B.J., Ishikawa E., Matsumura A.
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Journal Title
Pharmaceutics
Volume: 13
Pages: 1490～1490
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Polymer-stabilized elemental boron nanoparticles for BNCT: cell irradiation experiments.2021
Author(s)
Zaboronok A, Uspenskii S.A., Khaptakhanova P.A., Bekarevich R., Mechetina L.A., Volkova O.Yu., Kasatov D.A., Shchudlo I.M., Taskaev S.Yu., Mathis B.J., Kanygin V.V., Matsumura A.
Organizer
19th International Congress on Neutron Capture Therapy, Granada, Spain, 5-10 September, 2021. (Web開催). 口頭発表 (Oral presentation).
Int'l Joint Research
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