'Deep-etch' electron microscopic analysis of the actual mechanism of entry of cell-penetrating nanoparticles used for drug and gene-delivery into living cells
Project/Area Number |
25253004
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Physical pharmacy
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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)
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Project Period (FY) |
2013-05-31 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥45,760,000 (Direct Cost: ¥35,200,000、Indirect Cost: ¥10,560,000)
Fiscal Year 2015: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2014: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2013: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
|
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 / Electron microscopy / drug delivery / endocytosis / transfection / electron microscopy |
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.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Mitochondrial fission protein Drp1 regulates mitochondrial transport and dendritic arborization in cerebellar Purkinje cells.2016
Author(s)
Fukumitsu, K., Hatsukano, T., Yoshimura, A., Heuser, J., Fujishima, K. and Kengaku, M.
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Journal Title
Mol Cell Neurosci.
Volume: 71
Pages: 56-65
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology.2015
Author(s)
Ishikawa Y, Maeda M, Pasham M, Aguet F, Tacheva-Grigorova SK, Masuda T, Yi H, Lee SU, Xu J, Teruya-Feldstein J, Ericsson M, Mullally A, Heuser J, Kirchhausen T, Maeda T.
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Journal Title
Haematologica.
Volume: 100
Issue: 4
Pages: 439-51
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Mesoscopic Metal Nanoparticles Doubly Functionalized with natural and engineered lipidic dispersants for therapeutics2014
Author(s)
Murakami, T., Nakatsuji, H., Morone, N., Heuser, J. E., Ishidate, F., Hashida, M., Imahori, H.
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Journal Title
ACS Nano
Volume: 8
Issue: 7
Pages: 7370-7376
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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