開發可包覆細菌毒素的奈米載體應用於胃癌的治療

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 醫學院 > 基礎醫學研究所 > 博碩士論文 > Item 310903500/41366

請使用永久網址來引用或連結此文件: http://ir.cmu.edu.tw/ir/handle/310903500/41366

題名:	開發可包覆細菌毒素的奈米載體應用於胃癌的治療 Development of Nanoparticle-encapsulated bacterial toxin for the therapeutic effects of gastric cancer cells
作者:	呂侑侖
貢獻者:	基礎醫學研究所碩士班
關鍵詞:	彎曲桿菌;細胞致死腫脹毒素;奈米顆粒;胃癌 Campylobacter jejuni;Cytolethal distending toxin;Nanoparticle;Gastric cancer
日期:	2011-07-19
上傳時間:	2011-10-17 16:53:38 (UTC+8)
出版者:	中國醫藥大學
摘要:	彎曲桿菌是世界上最常引起人類腹瀉的致病菌之一，它可以在人體中引起許多不同的疾病，包括胃炎、腸胃炎、敗血症和嚴重的神經系統疾病，例如Guillian-Barr 症候群。在彎曲桿菌的眾多致病因子中，目前以細胞致死腫脹毒素 (cytolethal distending toxin, CDT)被研究的最為透徹，CDT會在真核細胞中造成細胞的腫脹，進而誘導細胞週期停滯在G2時期最後使得細胞走向凋亡的機制。先前的研究證實CDT是由三個次單元所組成，分別為CdtA、CdtB和CdtC，CdtA和CdtC這兩個次單元是扮演著結合到細胞膜表面的功能，而CdtB為細胞致死腫脹毒素中負責酵素活性的次單元，CdtB 具有能夠使DNA損傷的DNase I，並且能使細胞的週期暫停。在本研究中的另一個主角是奈米顆粒，奈米顆粒狹義的定義是其大小必須介於0.1-100nm之間，而奈米顆粒在近年來被廣泛的應用在許多不同的領域中，包括了生物醫學，光學和電子領域，正是因為它具有的潛在能力非常可觀，因此在許多的醫學研究中更是利用了它微小以及能夠攜帶藥物或是siRNA的能力來做更進一步深入的應用。本篇實驗中，我們利用奈米顆粒做為替代CdtA和CdtC這兩個結合次單元來運送CdtB進入細胞核中，在實驗中我們裡用了雷射掃描共軛焦顯微鏡(confocal laser scanning microscopy)觀察奈米顆粒包覆CdtB在細胞中的分布，發現了帶有CdtB的奈米顆粒的確有與細胞核重疊的現象產生，而另外在流式細胞儀的分析我們發現了奈米顆粒包覆CdtB的確實造成了細胞DNA的斷裂，而導致細胞週期停滯在G2/M時期，另外在西方轉漬法以及流式細胞儀的分析之下更發現了帶有奈米顆粒包覆CdtB最後會導致人類胃上皮細胞走向凋亡的途徑，而且比較細胞處理CDT全毒素而言，有更好的毒殺癌細胞之效力，因此本論文也證實奈米顆粒包覆CdtB可進一步應用於腫瘤細胞的治療。 Campylobacter jejuni (C. jejuni) is one of the most common cause of infectious diarrhea world-wide. This bacterium can induce various diseases in human including gastritis, gastroenteritis, septicemia, and serious neurological disorder like Guillian-Barr syndrome. The most important virulence factor of C. jejuni—cytolethal distending toxin (CDT), which can cause cell distending and induce cell-cycle arrest as well as apoptosis in eukaryotic cells. Previous studies have been demonstrated that CDT was composed by three subunits, CdtA, CdtB, and CdtC. Among those three subunits, CdtA and CdtC were served as the binding unit which associated with the cell surface. While the catalytic subunit CdtB, which was homology to type I deoxyribonuclease (DNase I) and phosphatidylinositol 3, 4, 5-triphosphate phosphatase enzymes, have the ability to degrade DNA. Translocation of CdtB into nucleus induced cell cycle arrested at G2/M phase. However, none of report explored the molecular mechanisms of CDT in its biological applications. Nanoparticle is defined as a microscopic particle with at least one dimension less than 100nm. Nanoparticle is widely used in researches, due to its wide variety of potential applications in various areas including biomedical, optical and electronic fields. Current researches indicated that nanoparticle could act as a carrier or encapsulated some drugs or siRNA into the target cell. In our preliminary investigation, we use chitosan/heparin nanoparticles to replace the binding subunit CdtA and CdtC for encapsulation of CdtB subunit and delivery nito host cells to achieve the same delivery effect as CdtA-CdtC complex. We developed novel pH-responsive CdtB/chitosan/heparin nanoparticles in the therapeutic effects in gastric cancer cells. The delivery efficiency of CdtB-loaded nanoparticles for tumor therapy is currently under investigating.
顯示於類別:	[基礎醫學研究所] 博碩士論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
cmu-100-9882011-1.pdf		2157Kb	Adobe PDF	460	檢視/開啟
index.html		0Kb	HTML	8	檢視/開啟

在CMUR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....