疊層組裝之奈米粒子於短鏈核苷酸遞送之研究

林修德

doi:10.6342/NTU.2008.02654

18.204.42.98，Hello！

Close
Search Quick Search Advanced Search Publication Search	Personal Service Member Login Searching History Use Bonus Card SYMSKAN
Browse Browse by University of Graduate Thesis Browse by Pinyin of Graduate Thesis Browse by Conference Proceedings Topic Browse by Conference Proceedings Publisher Browse by Pinyin of Conference Proceedings Browse by eBook Category Browse by eBook Topic Browse by eBook Publisher
Customer Services Authorize Airiti Recommend a Journal

Search Symbol (Half-width)	Description of Search Symbols
Space	"AND" indicates the intertwining of key terms used in a search
Double Quotation Marks ("") ( " " )	Double quotation marks indicate the beginning and end of a phrase, and the search will only include terms that appear in the same order of those within the quotations. Example: "image process" ： " image process "
?	Indicates a variable letter. Entering two ? will indicate two variable letters, and so on. Example: "Appl?", search results will yield apple, apply… e , appl y … ( (often used to English word searches) )
*	Indicates an unlimited number of variable letters to follow, from 1~n. Example: Enter "appl*", search results will yield apple, apples, apply, applied, application…(often used in English word searches) e , appl es , appl y , appl ied , appl ication … ( (often used to English word searches) )
AND、OR、NOT	Boolean logic combinations of key words is a skill used to expand or refine search parameters. (1) AND (1) AND: Refines search parameters (2) OR (2) OR: Expands search parameters (3) NOT: Excludes irrelevant parameters

DOI stands for Digital Object Identifier （ D igital O bject I dentifier ） ,
and is the unique identifier for objects on the internet. It can be used to create persistent link and to cite articles.

Using DOI as a persistent link

To create a persistent link, add「http://dx.doi.org/」「 http://dx.doi.org/ 」 before a DOI.
For instance, if the DOI of an article is 10.5297/ser.1201.002 , you can link persistently to the article by entering the following link in your browser: http://dx.doi.org/ 10.5297/ser.1201.002 。
The DOI link will always direct you to the most updated article page no matter how the publisher changes the document's position, avoiding errors when engaging in important research.

Cite a document with DOI

When citing references, you should also cite the DOI if the article has one. If your citation guideline does not include DOIs, you may cite the DOI link.

DOIs allow accurate citations, improve academic contents connections, and allow users to gain better experience across different platforms. Currently, there are more than 70 million DOIs registered for academic contents. If you want to understand more about DOI, please visit airiti DOI Registration （ doi.airiti.com ）。

Data Source

Health & Medical Care > Basic Medical Science
College of Medicine > Graduate Institute of Biochemistry and Molecularbiology

Bibliography Management Tool

Related Links

Report an Issue

Purchase Single Articles

Download PDF

疊層組裝之奈米粒子於短鏈核苷酸遞送之研究

Layer-by-Layer Assembly of Nanoparticles for Oligonucleotide Delivery

林修德 , Masters　　Advisor：張富雄　　

繁體中文 DOI： 10.6342/NTU.2008.02654

2-胍基-乙基-氨基甲酸；短鏈核苷酸；基因遞送；發炎反應；聚乙二醇； GEC-Chol ； oligonucleotide ； gene delivery ； inflammation ； polyethylene glycol

Abstract │ Reference (25) │ Altmetrics

Abstract 〈TOP〉

Parallel Abstract 〈TOP〉

The efficient gene delivery system is important both in therapeutic and laboratory research. The cationic materials can interact with negatively charged nucleic acids and assemble into several hundred nanometers in diameter complexes though the ionic interaction. However, there are several complications, for example, low delivery efficiency and poor stability, when applying these materials to in vivo gene delivery. In order to maintain the size of complexes and enhance the stability in vivo, previous studies have developed a strategy by using the highly hydrophilic polymer, polyethylene glycol (PEG), to modify the surface of particles hence improve the circulation time and stability.
GEC-Chol (2-guanidino-ethyl-carbamic acid-cholesterol) is a cholesterol-based cationic lipid. Previous studies reveal that, when GEC-Chol is mixed with cholesterol, they assemble into 100 nm particles. These particles are highly efficient in linear DNA delivery in in vitro experiments. In this study, we used FITC-labeled oligonucleotides as tracers and found that when N/P ratio of ODN and lipid was 3, the high delivery efficiency was observed. But if we added 10 % PEG-DOPE into the particle formulation, the delivery efficiency decreased dramatically. To solve the conflict between stability and efficiency, we bring up a strategy, post insertion, as a resolution. Briefly, we inserted PEG-modified lipids, PEG-DOPE, to the complexes after the particle of ODNs and cationic lipids formed, expected to reduce the particle size and increase the stability for in vivo applications. The result revealed that post-insertion particle had smaller particle size and higher stability. Using fluorescence microscopy and flow cytometry, we could observe that even lipid particles containing 10 % PEG-DOPE still retained the high delivery efficiency of FITC-labeled oligonucleotides in vitro. In order to detected particles in vivo, we add high quantum yield nanoparticles, quantum dots (QDs), to indicate the distribution of post-insertion particles. After analysis by confocol microscopy and agarose gel, it demonstrated that addition of QDs did not affect oligonucleotide encapsulation. This kind of particles did not induce inflammation in vivo and had high biocompatibility.
In this study, post-insertion particles containing 10 % PEG-DOPE have high delivery efficiency, and they do not induce obvious immune responses in vivo. Furthermore, if we elevate the PEG-DOPE ratio to 50 %, the nonspecific binding decreases evidently. The long and the short of it is that post-insertion particles are more suitable to be the carrier of nucleic acid drug in vivo than previous. In the future, we can add drugs or specific targeting molecules as tools for specific therapy and imaging in vivo.

Reference ( 25 ) 〈TOP〉

Brandwijk RJ, Griffioen AW, Thijssen VL (2007) Targeted gene-delivery strategies for angiostatic cancer treatment. Trends Mol Med 13(5): 200-9
連結：
Chan WH, Shiao NH, Lu PZ (2006) CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. Toxicol Lett 167(3): 191-200
連結：
Chang CF, Chen CY, Chang FH, Tai SP, Chen CY, Yu CH, Tseng YB, Tsai TH, Liu IS, Su WF, Sun CK (2008) Cell tracking and detection of molecular expression in live cells using lipid-enclosed CdSe quantum dots as contrast agents for epi-third harmonic generation microscopy. Optics express 16(13): 9534-48
連結：
Check E (2003) Harmful potential of viral vectors fuels doubts over gene therapy. Nature 423(6940): 573-4
連結：
Choi WJ, Kim JK, Choi SH, Park JS, Ahn WS, Kim CK (2004) Low toxicity of cationic lipid-based emulsion for gene transfer. Biomaterials 25(27): 5893-903
連結：

Altmetrics

〈TOP〉

E-mail ：

When an article is available to download, a notice will be sent to your mailbox address.

E-mail ：