'Deep-etch' electron microscopic analysis of the actual mechanism of entry of cell-penetrating nanoparticles used for drug and gene-delivery into living cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25253004
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: Heuser John 京都大学, 物質-細胞統合システム拠点, 教授 (40571815)
• Co-Investigator(Kenkyū-buntansha): Morone Nobuhiro 京都大学, 物質一細胞統合システム拠点, 客員教授 (50399680) ; Murakami Tatsuya 京都大学, 物質一細胞統合システム拠点, 准教授 (90410737)
• Project Period (FY): 2013-05-31 – 2016-03-31
• Keywords: 電子顕微鏡 / ドラッグデリバリー / エンドサイトーシス / トランスフェクション

Outline of Final Research Achievements

The basic purpose of this project was to visualize with the electron microscope (the EM) the mechanism of entry of the important cell-penetrating therapeutic agents available today, with the hypothesis that this entry is via endosome-rupture after cells have “endocytosed” the agents.We believed that visualizing endosome-rupture would be terribly important for understanding why these agents are effective, if they are, and for pointing the way for the development of future improved therapeutics in modern medicine. We felt that this was a vital medical goal, because it represents a 'bottleneck' between further industrial production of more modern therapeutics, and future clinical application of these new agents. These hypothesis so-called the “proton sponge” mechanism by polycationic polymers and the "endosome escape" by endosome-disrupting peptides were carefully tested by electron microscopy.

Free Research Field

細胞生物・生物物理学