| Project/Area Number |
22K12822
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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 90120:Biomaterials-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Receptor translocation / Target delivery / Size-changeable / size changeable / breast cancer / nanoparticles / Multidrug resistance / pH-sensitive / Nanoparticles |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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