https://scholars.lib.ntu.edu.tw/handle/123456789/83354
標題: | 大腸直腸癌之聚乙二醇-光感藥物的研發 | 作者: | 謝銘鈞 | 關鍵字: | 聚乙二醇;光感藥物;光動力;大腸直腸癌;PEG;photosensitizer;photodynamic therapy;colorectal cancer | 公開日期: | 30-十一月-2003 | 出版社: | 臺北市:國立臺灣大學醫學工程學研究所 | 摘要: | 光動力治療(photodynamic therapy)是屬於新興的癌症治療方式,主要是利用光感藥 物投藥後再給予照射適當波長的光激發細胞內的光感藥物,釋放的能量將血液中氧分子從 三態氧激發成成單相氧分子(singlet oxygen)或自由基(free radicals)來破壞細胞本體或 細胞的重要結構造成傷害使細胞死亡。雖然經研究發現光感藥物於腫瘤分佈的比例較正常 組織高,但仍會累積在皮膚,因此造成正常皮膚容易累積不必要的光感物質,這些物質如 果經照射陽光或其他光源後也會有光動力的效果,使得皮膚發炎、紅腫、潰爛的副作用產 生,病人在治療後生活上會有諸多不便。 我們利用聚乙二醇與光動力治療的藥物5-aminolevulinic acid (5-ALA)加以改質合成 新的光動力藥物,發展新的前驅光感藥物,以減少皮膚光敏感的副作用、增加光動力診斷 及治療的效果。研究成果發現5-ALA-PEG 確實會產生螢光,對於細胞也無明顯之毒性。這 是一個新的改質光感藥物。我們將進一步研究鍵結不同分子量PEG 的5-ALA 是否會被腸 胃道的細菌吞噬而產生PpIX,因為5-ALA 用於腸胃道診斷時,菌類同樣會產生PpIX 而影 響判斷結果,因此如果能利用接上不同分子量的PEG,使得5-ALA 無法被菌類轉換而癌細 胞可以轉換成PpIX,這樣可以大大增加癌症的診斷率,這也是新的診斷用光感藥物,未來 相當適合申請專利,於臨床及學術上均有相當重要之價值。我們期望能帶動國內醫藥的發 展,更能將國內生醫光電帶入一新的領域,極具臨床應用的價值。 Malignancy is the leading cause of mortality in Taiwan, and colon cancer accounted approximately 3000 deaths each year. Currently, there are several modalities of cancer treatments, including surgery, chemotherapy, and radiotherapy available clinically. Photodynamic therapy (PDT) is a promising new treatment for malignancy that has been recently introduced into the clinic practice. PDT involves the localization of a light-sensitive drug in the target tissue prior to illumination by laser using an appropriate wavelength. Exposure of targeted tissue containing a sufficient concentration of photosensitizer to irradiation of adequate wavelengths initiates photochemical reaction to generate single oxygen free radicals and other reactive species, consequently, causing cellular damage and tissue necrosis. This procedure has the potential to selectively destroy malignant tissues without causing serious damage to the adjacent normal structures if light dosimetry can be delivered with care. But the side effect of photosensitivity is still a problem to overcome. In this project, the new prodrug for colon-specific drug delivery will be synthesized by the covalent bonding of 5-aminolevulinic acid to poly (ethylene glycol) (PEG) to hydroxyl groups of PEG and subsequent conversion to activated ester. The aim of this study is to prepare a new photosensitizer with low side effect and high potential for photodynamic therapy. We reported the 5-ALA-PEG uptake by widr cells occurred and PpIX would be observed by fluorescent microscopy. We expect that the 5-ALA-PEG may be a new photosensitizer for colonrectal cancer diagnosis. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/29537 | 其他識別: | 912316B002017CC3 | Rights: | 國立臺灣大學醫學工程學研究所 |
顯示於: | 醫學工程學研究所 |
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912316B002017CC3.pdf | 184.88 kB | Adobe PDF | 檢視/開啟 |
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