| Project/Area Number |
19K16766
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Inoue Yuta 東京大学, 医学部附属病院, 届出研究員 (10802358)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 癌 / ナノメディシン / ドラッグデリバリーシステム |
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| Outline of Research at the Start |
我々は高分子ナノミセルを用いたドラッグデリバリーシステム(DDS)について研究を行っておりその過程で腫瘍血管が一過性に破綻しDDSが腫瘍組織に噴出する動的透過経路(Nano eruption)を発見した。本研究はDDSを腫瘍組織へ効率的に送達させるNano eruptionの促進と抑制の条件の解明を目的とする。TGF-β阻害薬、クロロキン、セレコキシブ、サリドマイド等を本研究の対象としてNano eruptionの制御と発生機序に迫る。
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| Outline of Final Research Achievements |
We have recently discovered dynamic extravasation through transient tumor vascular bursts. This phenomenon, named as nano-eruption (NE), increases accumulation of larger nanomicelles in tumors. To unveil the mechanisms and ultimately control NE, conditions that either provoke or inhibit NE is under investigation. Tumor-bearing mice were treated with either TGF-β inhibitor and chloroquine. The 30- or 70- nm fluorescent-labeled micelles were administered, and their tumor distribution was assessed over time with intravital microscopy.
TGF-β inhibitor increased the frequency, maximum area & velocity and duration time of NE. Chloroquine did not affect the frequency, but increased the maximum area & velocity and duration time of NE.
Our result demonstrated that different modulator drugs enhanced the different aspect of the NE, and the consequences are also dependent on the micelle size.
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| Academic Significance and Societal Importance of the Research Achievements |
Nano-eruption は 腫瘍血管系の一時的で不規則な開口部（dynamic vent）を介してドラッグデリバリーシステム（DDS）が腫瘍組織に送達する動的な血管透過性亢進現象である。Nano-eruptionの制御はDDSの効率を改善することが期待される。本研究からTGF-β阻害薬とクロロキンとナノメディシンのサイズを介したNano-eruptionの制御は、DDSの効率をさらに促進することが示唆された。
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