2019 Fiscal Year Annual Research Report
Development of a nano-pharmaceutical strategy for safely and effectively treating pregnant cancer patients
| Project/Area Number |
16H03179
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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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| Keywords | Placenta / Nanomedicine / Pre-term birth / Pre-eclampsia |
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| Outline of Annual Research Achievements |
The penetration of nano-sized agents through human placentawas studied to find the size cut-off size. When we perfused 10 nm gold NPs, the detected amount of gold nano-particles at the fetal side was increased time-dependently, and reached 4.58 % of administered dose after 60 minutes. Gold NPs with 20 nm were also detected dose at the fetal side (2.21%). Conversely, when 30 nm gold nano-particles were perfused, the detected dose from the fetal side was 0.05% of the administered dose after 60 minutes. These results suggest that there is cut-off of the size between 20-30 nm for nanomaterials to pass through the placenta.
Then, PEGylated-recombinant thrombomodulin (PEG-rTM) was prepared and used for treating pre-eclampsia. rTM was conjugated to 7-arm of 8-arm PEG (Mw: 40,000) and the remaining arm was conjugated with Cy5. In a mouse model of pre-eclampsia induced by AngII injection, PEG-rTM was found to accumulate in placenta, while Cy5-labeled rTM accumulated in liver. PEG-rTM effectively inhibited pre-eclampsia, and controlled body weight during fetal development. This was achieved by control of arterial pressure.
Indomethacin-loaded micelles (Indo/m) were also developed for pre-term birth treatment. Indo/m activate drug release inside macrophages but not in extracellular space. By using fluorescent-labeled Indo/m, we found they accumulated in inflammatory uterus. Thus, Indo/m effectively reduced inflammation in vivo and avoided 100% pre-term birth, whereas indomethacin was toxic and only inhibited pre-term birth in 40%. The pups born after Indo/m grow normally.
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| Research Progress Status |
令和元年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和元年度が最終年度であるため、記入しない。
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Research Products
(17 results)
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[Journal Article] , Enhanced MRI‐guided gadolinium (III) neutron capture therapy by polymeric nanocarriers promoting tumor accumulation and intracellular delivery.2020
Author(s)
C. Qin, X. Hou, T. Khan, N. Nitta, M. Yanagawa, Y. Sakurai, M. Suzuki, S. Masunaga, H. Tanaka, Y. Sakurai, H. Takahashi, I. Aoki, H. Yanagie, H. Cabral
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Journal Title
ChemNanoMat
Volume: -
Pages: -
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Single-stranded DNA-packaged polyplex micelle as adeno-associated-virus-inspired compact vector to systemically target stroma-rich pancreatic cancer.2019
Author(s)
T. A. Tockary, W. Foo, A. Dirisala, Q. Chen, S. Uchida, S. Osawa, Y. Mochida, X. Liu, H. Kinoh, H. Cabral, K. Osada, K. Kataoka
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Journal Title
ACS Nano
Volume: 13
Pages: 12732-12742
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Dexamethasone increases cisplatin-loaded nanocarrier delivery and efficacy in metastatic breast cancer by normalizing the tumor microenvironment.2019
Author(s)
J. Martin, M. Panagi, C. Wang, T. Khan, M. Martin, C. Voutouri, K. Toh, P. Papageorgis, F. Mpekris, C. Polydorou, G. Ishii, S. Takahashi, N. Gotohda, T. Suzuki, M. Wilhelm, V. Melo, S. Quader, J. Norimatsu, R. Lanning, M. Kojima, M. Stuber, T. Stylianopoulos, K. Kataoka, H. Cabral,
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Journal Title
ACS Nano
Volume: 13
Pages: 6396-6408
DOI
Peer Reviewed / Int'l Joint Research
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