| Project/Area Number |
16390408
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Nagoya University |
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Principal Investigator |
MIZUNO Masaaki Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (70283439)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Jun Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40158449)
TANUMA Sei-ichi Tokyo University of Science, School of Pharmacy, Professor, 薬学部, 教授 (10142449)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2005: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2004: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | structure-based drug / artificial cell / liposome / molecular target |
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| Research Abstract |
We have been developing the structure-based drug (SBD)-binding artificial cells to report some biological information to damaged cells. At first we designed the SBD for Fas or TRAIL by SBD design technology based on pharmacogenomics and computer technology. We also utilized liposomes which are artificial lipid bilayer vesicles considered to be useful as a drug delivery system, as artificial cells. Finally we made the SBD-binding artificial cells by combining the SBD with the liposome. In this study we investigated the cellular uptake, intracellular distribution and nuclear uptake of the SBD-binding artificial cells by molecular and fluorescent imaging techniques. We labeled each component of the artificial cells, lipids with octadecyl rhodamine B (R18), DNA with Fluorescein by covalent labeling or nick translation method. Then we exposed human glioma cells or other cancer cells including melanoma and breast cancer to labeled artificial cells in vitro and observed the intracellular dynamics by confocal laser microscope. A few hours later, the signals of lipids and DNA were detected on the surface of the cells and then were detected in the cytoplasm, particularly in the perinuclear area, but not in the nucleus. Some part of DNA-signals was detected at the cytoplasm apart from the artificial cells. Other DNA signals were detected in the chromosome area during cell division together with the artificial cells. On the other hand, we unfortunately found the instability of SBD or its binding artificial cells in in vivo. To maintain their character morphologically and biolologically, we needed the development of new technology for stability of SBD
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