1998 Fiscal Year Final Research Report Summary
Optimization of drug delivery system for antitumor agents based on the energy metabolism inhibition of tumor cells
| Project/Area Number |
09557197
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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 | 展開研究 |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokushima, Faculty of Pharmaceutical Sciences |
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Principal Investigator |
HARASHIMA Hideyoshi The University of Tokushima, aculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (00183567)
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| Co-Investigator(Kenkyū-buntansha) |
TERASAKI Tetsuya Tohoku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60155463)
SHINOHARA Yasuo The University of Tokushima, Faculty of Pharmaceutical Sciences, Associate Profe, 薬学部, 助教授 (60226157)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Drug delivery system / Liposomes / Tumor / Gene |
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| Research Abstract |
The objective of this study is to develop an optimum drug delivery system to increase antitumor effect by enhancing targeting efficiency of antitumor agents. An artificial carrier system for macromolecules to the nuclei was developed by using a pH-sensitive liposomes, which can enhance cytosolic escape of liposomally encapsulated macromolecules depending on the intra-endosomal pH decrease. The cytosolic delivery of macromolecules was confirmed by confocal laser microscopy. In addition, nuclear targeting of macromoleules was achieved by adding a nuclear localization signal (NLS) to the molecules. The FITC-labelled albumin, which can not be passively delivered to nucleus, was successfully targeted to nucleus by adding NLS.This system for intracellular control of macromolecules can be a basic strategy to manipulate intracellular trafficking of high molecular weight compounds. On the other hand, it has been shown that hexokinase type-II is specifically transcripted in tumor cells and this can be a target enzyme to be inhibited. We aimed to deliver DNA to inhibit the transcription of hexokinase-II in tumor cells. To achieve this, the quantitative assay system was required to measure DNA in intracellular organella such as nucleus. We have succeeded to develop a sound assay system to measure intra-nuclear DNA by applying PCR-method. This method provided us an interesting relationship between targeted nuclear DNA and transcription activity. By using this newly developed intracellular regulation system and quantitative assay method, we will be able to optimize rational drug carrier system to inhibit transcription in tumor cells.
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Research Products
(12 results)
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[Publications] M.Kuwajima, H.Harashima, M.Hayashi, S.Ise, M.Sei, K.Lu, H.Kiwada, Y.Sugiyama, K.Shima: "Pharmacokinetic analysis on the cardioprotective effect of 3- (2, 2, 2-trimethyl hydrazinium) propionate in mice : Inhibition of carnitine transporter in kidney." J.Pharm.Exp.Ther.(in press).
Description
「研究成果報告書概要(欧文)」より
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