| Project/Area Number |
16H03179
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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, 大学院工学系研究科(工学部), 准教授 (10533911)
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| Co-Investigator(Kenkyū-buntansha) |
永松 健 東京大学, 医学部附属病院, 准教授 (60463858)
持田 祐希 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 主任研究員 (60739134)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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| Keywords | Placenta / Nanomedicine / Size control / Pre-term birth / Pre-eclampsia / Placental barrier / Size effect / Preterm birth / Preeclampsia / Polymeric micelles / Star-shaped polymers / 高分子ナノメディシン / 胎盤輸送 / 抗癌治療 / 抗炎症治療 / マクロファージ標的 / Cancer / Anticancer drugs / ナノバイオ / ナノデバイス |
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| Outline of Final Research Achievements |
To identify the size of materials to pass through the placenta, we performed ex vivo human placental perfusion studies by using nano-sized agents. We found that there is cut-off of the size between 20-30 nm. Based on these results, we developed indomethacin-loaded micelles (Indo/m; 50 nm) for treatment of pre-term birth, PEGylated-recombinant thrombomodulin (PEG-rTM; 30 nm) for treating pre-eclampsia and size-controlled polymeric micelles loading (1,2-diaminocyclohexane)platinum (II) (DACHPt/m; 30 and 70 nm) for treating cancer. Indo/m were able to safely suppress pre-term birth in a model of uterine inflammation to promote the delivery of healthy pups. PEG-rTM was effective in a mouse model of pre-eclampsia induced by angiotensin II administration. Finally, both 30 and 70 nm DACHPt/m were active against breast cancer models. However, only 70-nm DACHPt/m could avoid placenta accumulation, allowing the delivery of normal pups.
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| Academic Significance and Societal Importance of the Research Achievements |
Our results indicate the importance of size control of nanomedicines for generating safe therapies during pregnancy. We have patented these findings, and are looking to translate the developed systems to clinical application in collaboration with industry, expecting to benefit pregnant patients.
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