• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2019 Fiscal Year Final Research Report

New concept for bone and soft tissue sarcoma treatment by low-pH sensitive liposome

Research Project

  • PDF
Project/Area Number 16K10856
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionMie University

Principal Investigator

Asanuma Kunihiro  三重大学, 医学部附属病院, 講師 (20378285)

Co-Investigator(Kenkyū-buntansha) 吉村 哲郎  三重大学, 工学研究科, 特任教授(研究担当) (30035472)
Project Period (FY) 2016-04-01 – 2020-03-31
Keywordssarcoma / pH / acidity
Outline of Final Research Achievements

pH in bone and soft tissue tumor is below 6.9. We designed liposome based on next three concept, 1) long stability and escape from immune and reticuloendothelial system by adding polyethyleneglycol, 2)infiltration from abnormal vascular and accumulation in tumor tissue by under 100nm of diameter, 3) release drugs below pH6.7. We successfully produced new concept liposome and this liposome accumulated tumor tissue using mouse xenograft model. However, by intravascular injection of methotrexate encapsulated liposome induced mouse death. From this results, this liposome had a toxicity by vascular injection. In cell experiment, this liposome deliver and release drugs by activation of low pH and deliver drugs inside of cells by endocytosis irrelatively pH. This liposome has 2 delivery system based on pH level.

Free Research Field

sarcomas

Academic Significance and Societal Importance of the Research Achievements

癌に対する抗癌剤の高い効果を期待するには、高濃度の抗癌剤をがん組織に暴露させる必要がある。しかし、抗癌剤濃度があがれば、副作用が増加する。副作用の軽減方法は、副作用の少ない癌細胞の標的、薬物の種類を作成するか、あるいは抗癌剤を癌細胞選択的に集積させ、全身への濃度を少なくさせるか、に分けられる。本研究は後者であり、腫瘍の特異性として肉腫組織内の酸性度(ph6.9以下)に注目し、ph6.7前後で薬剤を放出するリポソームを開発し、抗癌剤であるメソトレキセートの封入に成功した。マウスに移植した肉腫には集積性を示したが、一定量の投与で毒性を示した。今後、リポソームのさらなる改良が必要である。

URL: 

Published: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi