具標靶功能之新樹枝狀聚胺基甲酸酯－葉酸共軛物之合成及其在基因傳遞之研究

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Dissertations and Theses > Item 310902800/26109

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/26109

Title:	具標靶功能之新樹枝狀聚胺基甲酸酯－葉酸共軛物之合成及其在基因傳遞之研究 Synthesis and Characterizations of New Targeting Poly(urethane-amine)Dendrimer-Folic Acid Conjugate and Study On Gene Delivery
Authors:	沈怡君
Contributors:	生物科技系暨研究所蕭明達
Keywords:	基因治療樹枝狀型陽離子非病毒性載體轉染 Gene therapy Cationic dendrimer Non-viral vector Transfection
Date:	2011
Issue Date:	2012-11-29 11:35:42 (UTC+8)
Abstract:	成功的基因治療須有一個良好的傳遞載體，一般用於傳遞基因的載體可分為兩大類:病毒型載體及非病毒型載體。本研究目的在於合成一個低細胞毒性及生物可分解性的新樹枝狀陽離子型高分子載體，使其能讓帶負電的質體DNA 分子藉由靜電作用力自組裝的形成奈米大小的複合物，這樣的複合物就能使細胞以胞飲的方式進入到細胞內而達到治療效果。近年來葉酸已被廣泛使用為具癌症標靶的標的試劑，並大量使用於藥物傳遞系統中。在此研究，我們利用證實擁有基因轉染潛力的新樹枝狀聚胺基甲酸酯(PUAD)與葉酸接枝(PUAD-OH-FA)。PUAD為低毒性且水解性優異的樹枝狀高分子，在酸性環境下可因質子化帶有正電荷。因此可與帶有負電荷的DNA 透過靜電作用力結合形成複合體。我們除了合成具癌標的PUAD-OH-FA外，另外合成了不具癌標的PUAD高分子作為對照組。並以NMR與FT-IR來做基本性質的探討。之後，我們將PUAD-FA 與質體DNA 在不同的重量比下製備複合體，再以電泳膠片分析複合體所包覆質體DNA的效能。希望具接枝葉酸的PUAD具有標靶癌細胞效果，可做為新穎癌標基因傳遞載體的發展潛力。 The successful gene therapy need an ideal gene delivery vector. Two popular vectors for gene delivery under intensively studied are viral carriers and non viral ones. In non-viral vector, the most important requirement is the low cytotoxicity and high transfection efficiency. The purpose of this study is to design and synthesize new cationic dendrimers with a low cell toxicity and high biodegradability. The new material can condense negatively charged plasmid DNA by electrostatic force to self-assembly of nano-sized complexes. This nano-complexes can achieve the therapeutic effect of intracellular through endocytosis. Folic acid has been used as a targeting ligand for drug delivery systems for cancer therapy in past years. In this study, we use poly(urethane-amine) dendrimer (PUAD) to conjugate folic acid molecules ..We synthesized PUAD-OH-FA as a tumor-targeting gene carrier and PUAD as a reference. The chemical structures of PUAD-OH-FA and PUAD were indentified by NMR and FT-IR. The various weight ratios of PUAD-OH-FA /DNA and PUAD/DNA complexes were prepared. Particle size and zeta potential of complexes were analyzed by dynamic light scattering. Agarose gel electrophoresis was used to evaluate the characterizations of PUAD-OH-FA /DNA and PUAD/DNA prepared from different weight ratios. Thus, PUAD-OH-FA is potentially developed as a gene carrier specifically targeting to tumor cells.
Relation:	校內校外均不公開，學年度：99，96頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	1471	View/Open

Loading...