Study of cellular uptake and cancer therapy with torpedo-shaped nanocapsule

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15334
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ueda Motoki 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (10615040)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: ペプチド集合体 / アスペクト比 / ドラッグデリバリー / ソフトマター / がん治療 / 両親媒性ポリペプチド / 細胞内取込 / エンドサイトーシス

Outline of Final Research Achievements

Multiple tubular assemblies with the same diameter and different lengths were prepared from amphipathic polypeptide and were used to study the effect of the aspect ratio of the material on cellular uptake behavior. The results showed that tubular assembly with a diameter of 80 nm and a length of 200 nm showed the fastest cellular uptake, due to its suitable size for the clathrin-mediated endocytosis pathway. After an anticancer drug was encapsulated in this tubular assembly, the mouths of the tube were sealed with another sheet-like peptide assembly. This drug-loaded assembly was administered to cancer-baring mice. As a result, the tumor accumulation and the therapeutic effect of the drug-loaded assembly were confirmed.

Free Research Field

バイオマテリアル

Academic Significance and Societal Importance of the Research Achievements

これまで、無機粒子などを用いてその形状およびアスペクト比が及ぼす効果について報告されてきたが、今回初めて中空材料においてアスペクト比の制御および薬剤内包に成功し、実際に球状材料などに比べて素早い細胞内取込を示すことを明らかにし、DDSキャリアとしての有用性を示した。本研究はDDS分野において材料形状がもたらす機能の重要性を示すものであり、「形状・アスペクト比」が、これまでに確立されてきた「サイズ」「表面電荷」「表面修飾」に続く薬剤輸送キャリアの設計指針の一つとなることを決定する重要な成果である。