| Project/Area Number |
22K20524
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0501:Physical chemistry, functional solid state chemistry, organic chemistry, polymers, organic materials, biomolecular chemistry, and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2022-08-31 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | Raman spectroscopy / SERS / Drug delivery / Single-cell endoscopy / Nanoparticles / Raman psectroscopy / SN-38 / Nanoparticle / Drug delivery systems / Single cell endoscopy |
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| Outline of Research at the Start |
Probing the intracellular metabolism of the newly established nanomedicine is crucial for assessing the efficiency of the drug delivery systems. In this work, we aim to be the first to elucidate the intracellular metabolism of SN-38 anticancer nanoprodrugs based on the single cells SERS endoscopy technique. An overall understanding of the intracellular particle degradation, drug molecules diffusion/accumulation, as well as their interaction with biomolecular targets, is expected to pave the way for the further development of advanced drug delivery strategies.
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| Outline of Final Research Achievements |
In this work, metal organic framework coated nanowire endoscopy was developed and applied for detection of anticancer drug metabolism inside cancer cells. The developed technique combines the high spatiotemporal resolution and non-invasiveness of the endoscopic approach, and high-selectivity of metal organic framework coating. This enables a real-time localization of SN-38 released from irinotecan anticancer drug by esterase enzyme-mediate cleavage inside HeLa cancer cells. We were able observed the release of SN-38 inside cytoplasm, followed by their diffusion to the nucleus where SN-38 molecules interact with topoisomerase and DNA complexes to inhibit DNA replication. This approach shows potential for specifically tracking drug molecules and exploring their intracellular metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
生きた細胞内での薬物分子の動態と分布を理解することは、新しい治療法の設計と発見にとって重要である。我々が開発した単一細胞解析アプローチは、内在性生体分子からの干渉なしに、複雑な細胞内環境でSN-38薬物分子を選択的に追跡および監視することを可能にした。この方法は、広範囲の薬物分子の代謝のリアルタイム監視に応用でき、薬物分子設計のさらなる開発と改善に貢献できる。
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