Development of a nano-pharmaceutical strategy for safely and effectively treating pregnant cancer patients

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H03179
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: The University of Tokyo
• Principal Investigator: Cabral Horacio 東京大学, 大学院工学系研究科(工学部), 准教授 (10533911)
• 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)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: Placenta / Nanomedicine / Size control / Pre-term birth / Pre-eclampsia

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.

Free Research Field

Nanomedicine

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.