Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization
碩士 === 高雄醫學大學 === 醫藥暨應用化學研究所 === 96 === Folic acid has been used as a targeting ligand for drug delivery systems for cancer therapy in past years. In this study, we use polyethylene glycol (PEG, Mw~3400) as a spacer to conjugate folate acid molecules with chitosan (FA-PEG-Chi). Chitosan has been pro...
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ndltd-TW-096KMC055370272015-11-25T04:05:13Z http://ndltd.ncl.edu.tw/handle/62667484671546107690 Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization 製備及分析具葉酸調控之標靶型幾丁聚醣基因載體 Yu-Lun Lo 羅于倫 碩士 高雄醫學大學 醫藥暨應用化學研究所 96 Folic acid has been used as a targeting ligand for drug delivery systems for cancer therapy in past years. In this study, we use polyethylene glycol (PEG, Mw~3400) as a spacer to conjugate folate acid molecules with chitosan (FA-PEG-Chi). Chitosan has been proved nontoxic, biocompatible, biodegradable, and can be protonated in an acidic condition (pH<7) because of pKa=6.5. Therefore Chitosan can form a complex with counter anionic DNA through electrostatic interactions. We synthesized FA-PEG-Chi as a tumor-targeting gene carrier and mPEG-Chi as a reference. The grafting molar percentages of FA-PEG and mPEG are 15.7% for FA-PEG-Chi and 10.6% for mPEG-Chi by 1H NMR. The different weight ratios of FA-PEG-Chi/DNA and mPEG-Chi/DNA nanoparticles were prepared. Particle size and zeta potential of nanoparticles were analyzed by dynamic light scattering. Agarose gel electrophoresis and Picogreen assay were adapted to test the DNA encapsulation in polyplexes prepared from different weight ratios. The results showed that DNA could well encapsulated when the weight ratio of a polyplex is over 1. In vitro test, both FA-PEG-Chi/DNA and mPEG-Chi/DNA didn’t show high cytotoxicity in KB cells. Besides, FA-PEG-Chi/DNA had better transfection efficiency than mPEG-Chi/DNA. Thus, FA-PEG-Chi is potentially developed as a gene carrier specifically targeting to tumor cells. Li-Fang Wang 王麗芳 2008 學位論文 ; thesis 83 zh-TW |
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碩士 === 高雄醫學大學 === 醫藥暨應用化學研究所 === 96 === Folic acid has been used as a targeting ligand for drug delivery systems for cancer therapy in past years. In this study, we use polyethylene glycol (PEG, Mw~3400) as a spacer to conjugate folate acid molecules with chitosan (FA-PEG-Chi). Chitosan has been proved nontoxic, biocompatible, biodegradable, and can be protonated in an acidic condition (pH<7) because of pKa=6.5. Therefore Chitosan can form a complex with counter anionic DNA through electrostatic interactions.
We synthesized FA-PEG-Chi as a tumor-targeting gene carrier and mPEG-Chi as a reference. The grafting molar percentages of FA-PEG and mPEG are 15.7% for FA-PEG-Chi and 10.6% for mPEG-Chi by 1H NMR.
The different weight ratios of FA-PEG-Chi/DNA and mPEG-Chi/DNA nanoparticles were prepared. Particle size and zeta potential of nanoparticles were analyzed by dynamic light scattering. Agarose gel electrophoresis and Picogreen assay were adapted to test the DNA encapsulation in polyplexes prepared from different weight ratios. The results showed that DNA could well encapsulated when the weight ratio of a polyplex is over 1. In vitro test, both FA-PEG-Chi/DNA and mPEG-Chi/DNA didn’t show high cytotoxicity in KB cells. Besides, FA-PEG-Chi/DNA had better transfection efficiency than mPEG-Chi/DNA. Thus, FA-PEG-Chi is potentially developed as a gene carrier specifically targeting to tumor cells.
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Li-Fang Wang |
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Li-Fang Wang Yu-Lun Lo 羅于倫 |
author |
Yu-Lun Lo 羅于倫 |
spellingShingle |
Yu-Lun Lo 羅于倫 Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization |
author_sort |
Yu-Lun Lo |
title |
Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization |
title_short |
Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization |
title_full |
Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization |
title_fullStr |
Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization |
title_full_unstemmed |
Folate-Mediated Chitosan as a Gene Carrier for Cancer Targeting:Preparation and Characterization |
title_sort |
folate-mediated chitosan as a gene carrier for cancer targeting:preparation and characterization |
publishDate |
2008 |
url |
http://ndltd.ncl.edu.tw/handle/62667484671546107690 |
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