Development of a novel multifunctional nanoliposome-based system for maintaining active agent concentration in tumor tissue during boron-neutron capture therapy
| Project/Area Number |
23K06738
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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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) |
石川 栄一 筑波大学, 医学医療系, 教授 (30510169)
白川 真 福山大学, 薬学部, 講師 (40707759)
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, 医学医療系, 准教授 (80794635)
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| Project Period (FY) |
2023-04-01 – 2026-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2024: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | liposomes / glioma / BNCT / carboranes / nanoparticles / boron / gold / active tumor targeting / tumor targeting |
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| Outline of Research at the Start |
Synthesis and application of liposome-based theranostic nanoparticle complex superior to existing compounds for boron neutron capture therapy (BNCT) implemented by our research group will solve the problem of large boron amount delivery and its retention in tumor cells during neutron irradiation needed for successful neutron capture reaction and dosimetry in cancer treatment using BNCT.
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| Outline of Annual Research Achievements |
In the 2023 fiscal year, we completed the synthesis of liposomes as planned, setting the stage for the integration of the active tumor targeting component, which is scheduled for the final stage before animal experiments. Gold nanoparticles were employed at varying concentrations to create complex liposomes. We examined the composition using transmission electron microscopy (TEM), which helped us determine the optimal amount of gold necessary for effective targeting linkage and visualization. All necessary components have been prepared or synthesized for additional modifications of the liposomes and the inclusion of boron compounds in both the water phase and the bilipid layer. Several boron compounds/nanoparticles were evaluated as potential integrants for the liposomes. Notably, three types of carboranes and boron-containing magnetic nanoparticles demonstrated adequate cellular tolerability and effective boron accumulation in tumor cells. Initially, human T98 glioma cells were used in these experiments. The liposomes remained stable in aqueous solutions for weeks to months, allowing for ongoing TEM analysis during their storage. Additional experiments were conducted to examine irradiation settings at the accelerator, using large animals and a low-molecular-weight boron compound. Various aspects of these irradiation experiments were analyzed to inform future implementations with liposomes. Although the study was delayed due to one of the researchers transferring to another university, it will continue as planned, as he will still participate in the study.
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| Current Status of Research Progress |
Current Status of Research Progress
3: Progress in research has been slightly delayed.
Reason
The study was delayed because one of the researchers transferred to another university. For liposome synthesis, some additional equipment was needed, which was purchased at the new location. However, this acquisition took some time. Despite these delays, the study will continue as planned.
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| Strategy for Future Research Activity |
In the next fiscal year, we aim to advance our work by refining the synthesis of complex liposomes, incorporating gold nanoparticles for both diagnostic purposes and linkage to the targeting system. Our research will extend to developing an experimental animal tumor model tailored for liposome application and conducting in vitro evaluations to assess delivery mechanisms, using the same cell lines planned for the animal studies. Additionally, we will focus on the accumulation of core compounds, dosimetry, and analyzing the tumor cell-killing effects of neutrons irradiated from an accelerator or nuclear reactor on cells with accumulated complex liposomes. We will also select the most suitable cell lines for these experiments and initiate animal studies to evaluate nanoliposome toxicity.
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Report
(1 results)
Research Products
(1 results)
