| 研究課題/領域番号 |
20K07672
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| 研究機関 | 筑波大学 |
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研究代表者 |
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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| 研究分担者 |
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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| 研究期間 (年度) |
2020-04-01 – 2023-03-31
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| キーワード | BNCT / glioma / nanoparticles / tumor targeting |
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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
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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| 今後の研究の推進方策 |
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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| 次年度使用額が生じた理由 |
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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| 備考 |
[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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