| DC 欄位 |
值 |
語言 |
| DC.contributor | 化學學系 | zh_TW |
| DC.creator | 黃安琪 | zh_TW |
| DC.creator | AnChi Huang | en_US |
| dc.date.accessioned | 2012-7-23T07:39:07Z | |
| dc.date.available | 2012-7-23T07:39:07Z | |
| dc.date.issued | 2012 | |
| dc.identifier.uri | http://ir.lib.ncu.edu.tw:88/thesis/view_etd.asp?URN=992203052 | |
| dc.contributor.department | 化學學系 | zh_TW |
| DC.description | 國立中央大學 | zh_TW |
| DC.description | National Central University | en_US |
| dc.description.abstract | 此論文有兩篇主題，首先是合成抗癌藥物Bortezomib的衍生物進行對肝癌（Hepatocellular carcinoma）細胞抑制的探討。肝癌是臺灣男性中最常發生的腫瘤。其治療方法多侷限於手術；化療則是較後期病患的主要治療方式。但這些一般、傳統的治療方法在延長病患的生命上，效果很有限。因此尋找有效的肝癌治療方法，仍有迫切的需要。我們將藉由化學合成一系列Bortezomib的衍生物，再由細胞實驗結果探討其結構與活性的關聯。
第二個主題是合成奈米載體（nanocarrier），以照光可斷裂的linker（Photocleavable Linker）為中心，兩端分別接有RNAi及聚乙二醇（poly (ethylene glycol)），使其進入細胞後進行基因抑制。RNAi技術在藥物研究中應用日趨廣泛，可以解決在藥物開發中的一些瓶頸問題，如藥物的標靶作用、標靶效用的強化，從而節省時間和資金，提高成功率。在此，我們合成一個結構簡單的載體，期望設計出一個以聚乙二醇為主體並且使其具有穿膜載體之功能，並透過細胞實驗觀察其效果。
| zh_TW |
| dc.description.abstract | Topic 1：
Hepatocellular carcinoma (HCC) is the most deadly cancer among the males in Taiwan. It is also one of the most difficult tumors to treat. For the patients in advanced stage, relapse or metastatic tumors, chemotherapy is still the main treatment. However, traditional chemotherapeutic agents did not show acceptable responses in prolonging patients’ survival in HCC.
Bortezomib, a proteasome inhibitor, has been clinically approved for use in the treatment of multiple myeloma and mantle cell lymphoma. It also has been shown to reduce the acticity of CIP2A and cause cell apoptosis. Here, we based on bortezomib, prepared a series of novel compounds and conducted the SAR study. The results showed that compound 1a was able to repress the CIP2A activity and leading to cell apoptosis as bortezomib, but less inhibitive effects on proteasome activity. Such finding should be helpful in the future design of new CIP2A inhibitors.
Topic 2：
RNA interference (RNAi) has been the focus in recent biological studies and shown its potential in medicine. However, the delivery of small interfering RNA (siRNA) to the targeted cells and the penetration of the cell membrane remain the major hurdles for the application of RNA interference in therapeutics.
To overcome this challenge, we synthesized a siRNA nanocarrier which combined polyethylene glycol (PEG), photocleavable linker (PL) and thiolated siRNA. Their ability in achieving the gene silencing, i.e. penetrating the cell membrane and knocking down the expression of GFP gene, was screened. The initial positive results suggest that to the formation of the well-shaped particles is important in the penetration of the cell membrane, although our siRNA-PL-PEG nanocarriers are free of the conventional cationic lipid or polymers as the counter ions.
| en_US |
| DC.subject | 基因沉默 | zh_TW |
| DC.subject | 肝癌 | zh_TW |
| DC.subject | Bortezomib | en_US |
| DC.subject | siRNA | en_US |
| DC.subject | CIP2A | en_US |
| DC.subject | RNAi | en_US |
| DC.subject | Hepatocellular carcinoma | en_US |
| DC.title | 合成Bortezomib衍生物抑制肝癌細胞與siRNA nanocarrier之合成和細胞穿透研究 | zh_TW |
| dc.language.iso | zh-TW | zh-TW |
| DC.title | Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition and Synthesis of Nanocarriers for the Efficient Intracellular siRNA Delivery and Gene Silencing | en_US |
| DC.type | 博碩士論文 | zh_TW |
| DC.type | thesis | en_US |
| DC.publisher | National Central University | en_US |