| 研究課題/領域番号 |
22K12822
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分90120:生体材料学関連
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| 研究機関 | 熊本大学 |
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研究代表者 |
Lee Ruda 熊本大学, 産業ナノマテリアル研究所, 准教授 (00802050)
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| 研究期間 (年度) |
2022-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2024年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円)
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: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
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| キーワード | Receptor translocation / Target delivery / Size-changeable / size changeable / breast cancer / nanoparticles / Multidrug resistance / pH-sensitive / Nanoparticles |
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| 研究開始時の研究の概要 |
Compared to other breast cancer subtypes, epidermal growth factor receptor (EGFR) has been reported to be overexpressed up to 78% of triple-negative breast cancer (TNBC). Aberrantly expressed EGFR undergoes direct nuclear translocation and a new role of nucleus EGFR (nEGFR) signaling in conferring acquired multidrug resistance (MDR). The cell nucleus-targeted drug delivery is a promising strategy for anticancer therapy, but MDR nucleus targeted drug delivery has been challenging due to the cytoplasm-located drug pumped out by MDR transporters.
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| 研究実績の概要 |
In 2023, the objective was to assess the characteristics of nanoparticles (NPs) at the cellular level. Both micelles and NPs were labeled with Alexa 488 and Cy5.5, respectively. Co-localization was confirmed before and after internalization into TNBC/MDR cell cytosol. Approximately 6 hours post-internalization, the micelle signal was observed within the nucleus, while the NP signal remained in the cytosol. We observed time-dependent signal clearance and nucleus degradation during our investigation.
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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
The cellular internalization and nucleus target images were obtained. Furthermore, the translocation of EGFR was confirmed by super-resolution imaging microscopy (STORM). To step forward fast, animal orthotropic breast cancer model was set up the condition. To induce the tumor, the parental and drug-resistant cell lines inoculated number and growth condition was confirmed.
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| 今後の研究の推進方策 |
In 2024, an animal study will be conducted to assess the pharmacokinetic properties of size-adjustable nanoparticles (NPs). The animal protocol has been duly approved by the Institutional Animal Care and Use Committee (IACUC) of Kumamoto University in 2023. In order to demonstrate the considerable promise of nucleus-targeted drug delivery, the effectiveness of a scramble peptide will be assessed concurrently. Comprehensive evaluations will encompass histological analysis, liver function testing (to ascertain NP cytotoxicity), and assessment of NP blood circulation. Additionally, efforts will commence to compile the findings for publication in a scholarly journal.
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