2023 Fiscal Year Final Research Report
Label-free intracellular dynamics investigation of carrier-free nanoparticle-based drug delivery systems
| 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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| Keywords | Raman spectroscopy / SERS / Drug delivery / Single-cell endoscopy / Nanoparticles |
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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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| Free Research Field |
Nanomaterials
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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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