| Project/Area Number |
25750172
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | The University of Tokyo |
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Principal Investigator |
CABRAL Horacio 東京大学, 工学(系)研究科(研究院), 准教授 (10533911)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ドラッグデリバリー / 環状RGDペプチド / ナノ粒子のサイズ / アクティブターゲティング / 高分子ミセル / グリオーマ / 腫瘍ターゲティング / 制がん剤 |
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| Outline of Final Research Achievements |
The aim was to evaluate the size effect of ligand-installed nanomedicines in their ability to target solid tumors. Drug-loaded micelles having 30-, 50-, 70- and 100-nm diameter were prepared, and conjugated with cyclic-RGD (cRGD) peptide for targeting of tumors overexpressing avb3 and avb5 integrins. cRGD-installed micelles (cRGD/m) showed comparable stability and drug release rates. The in vitro activity of cRGD/m against monolayer culture of glioma U87-MG cells showed that all cRGD/m had comparable cytotoxicity. In vivo, 30- and 50-nm cRGD/m suppressed the growth of U87-MG xenografts, while larger cRGD/m failed to show antitumor activity. Tumor accumulation was around 8% of injected dose per gram of tissue for 30- and 50-nm cRGD/m, whereas larger cRGD/m were lower than 2%. In vivo CLSM showed cRGD/m with 30-nm penetrated into U87-MG tumors, whereas 70-nm cRGD/m did not extravasate, indicating a size-mediated active transport mechanism.
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