| 研究課題/領域番号 |
22K20524
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| 研究種目 |
研究活動スタート支援
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| 配分区分 | 基金 |
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| 審査区分 |
0501:物理化学、機能物性化学、有機化学、高分子、有機材料、生体分子化学およびその関連分野
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| 研究機関 | 北海道大学 |
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研究代表者 |
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| 研究期間 (年度) |
2022-08-31 – 2024-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
2,860千円 (直接経費: 2,200千円、間接経費: 660千円)
2023年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
2022年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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| キーワード | Drug delivery / Nanoparticle / Raman spectroscopy / SERS / Single-cell endoscopy / SN-38 / Drug delivery systems / Single cell endoscopy / Nanoparticles |
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| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
In AY2022, we focused on 1) functionalizing nanoprodrugs and 2) developed the method based on Raman spectroscopy for intracellularly label-free analysis of nanoprodrugs dynamics. The surface of SN-38 nanoprodrugs was decorated with biotin-modified liposomal membranes to enhance the internalization of cancer cells and target specific cellular compartments. For the analysis of intracellular drug dynamics based on single-cell SERS endoscopy, we successfully coated silver nanowire (AgNW) probes of the endoscopy system with ZIF-8 metal-organic framework, enabling the selective detection of molecules based on their molecular sizes and hydrophobicity. The developed method is able to detect the conversion of irinotecan prodrug into SN-38 active drug molecule (Advanced optical materials, 2023 accepted).
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Most of the research objectives, including the development of SN-38-based DDS and an approach for intracellular dynamic studies, are completed during the first year of implementation. The functionalization of SERS endoscopy probe with ZIF-8 allows the selective detection of drug molecules and its metabolite in the highly complex intracellular environment, which is extremely challenging. We are now progressing to investigating the nanoprodrugs intracellularly based on the successfully developed approach.
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| 今後の研究の推進方策 |
For AY2023, ZIF-8 modified AgNW single-cell SERS endoscopy developed in AY2022 will be utilized to study SN-38 nanoprodrugs intracellular dynamics. After the SN-38 nanoprodrugs are administrated to cancer cells, their internalization and drug molecule dissolution from nanoparticles will be monitored by fluorescent and Raman spectroscopy techniques. Then, using SERS endoscopy, the conversion of SN-38 prodrug will be monitored at the specified intracellular location over time. After a clear knowledge of the intracellular dynamics of SN-38 nanoprodrugs is obtained, the project will investigate the dynamics of DDS in 3D tumor models.
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