Influence on the plasma membrane induced by microparticles and its relation to the cellular internalization of microparticles

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K01399
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Meiji University
• Principal Investigator: KATO Noritaka 明治大学, 理工学部, 専任教授 (90329110)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 細胞膜 / 生体材料 / 多光子励起顕微鏡 / 微粒子 / 薬物送達システム / エンドサイトーシス

Outline of Final Research Achievements

HeLa cells were used to clarify the internalization pathway of particles with a diameter of 1 um. The major pathway depended on the surface chemistry of the particle. The PEGylated particles were internalized via macropinocytosis (MPC), and the cationic particles with the positively-charged surface penetrated through the plasma membrane. Since the damage of the plasma membrane was observed after the internalization of the cationic particles, the plasma membrane was suggested to adhere to the cationic particles electrostatically and be cut off upon their entry to the cell. The PEGylated particles that do not damage the membrane have poor internalization efficiency, but it is expected that the efficiency will be improved by decreasing the particle size. Thus, we showed the possibility of intracellular delivery using MPC. Furthermore, we showed that a multi-photon excitation microscope can be used to perform a more sensitive detection of the cell-membrane damage than the current way.

Free Research Field

材料物性

Academic Significance and Societal Importance of the Research Achievements

粒子の内在化経路の解明は、ドラッグキャリアを用いた薬物送達システムの開発に貢献できる。PEG化粒子の多くが腫瘍細胞に特徴的なマクロピノサイトーシスにより取り込まれることが明らかになったため、腫瘍細胞への薬物送達システムの開発に貢献できる。また、粒子の表面状態で細胞毒性が異なることを明らかにしたので、低毒性のドラッグキャリアの設計の指針を与える。さらに、従来法では検出できない僅かな細胞膜の乱れを検出する方法を開発したので、これまで見過ごされてきた膜損傷機構や修復機構などを発見できる可能性を秘めており、本研究で得られた成果は、薬物送達システムへの応用だけでなく、基礎生命科学への貢献も可能である。