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標題: | 光穩定性與生物相容性碳量子點材料於癌症治療之應用 Application of photostable and biocompatible carbon-dot aggregates in cancer therapy |
作者: | Pei-Ying Lai 賴佩瑩 |
指導教授: | 張煥宗(Huan-Tsung Chang) |
關鍵字: | 碳量子點,螢光染劑,微脂體,奈米藥物傳輸系統, carbon-dot aggregates,reversible fluorescent photoswitching,liposome,cisplatin,drug delivery system, |
出版年 : | 2017 |
學位: | 碩士 |
摘要: | 由於次微米尺寸的微脂體可有效延長藥物體內半衰期及增加藥效,已被認為是良好藥物載體,然而因其結構限制,通常僅能承載親水性的藥物,且對於溫度敏感,不易保存,甚至不易以粉末型態運輸。另外,其本身不具有螢光,並不利於藥物追蹤及探討。本篇論文利用非異相性修飾之碳量子點自組裝形成類似微脂體的次微米囊泡結構,稱之為聚集碳量子點(C-dot aggregates),此材料在 105 W汞燈照射下,可維持 10 小時以上的高光穩定性,並且具可調式激發放光特性,可即時於生物體中進行藥物動向追蹤,也能長期觀察藥物的生物蓄積效應。此外,聚集碳量子點於癌細胞之半致死劑量(Half maximal inhibitory oncentration, IC50)高於市售脂溶性染劑(3,3'-Dioctadecyloxacarbocyanine Perchlorate, DiO)6000 倍,並具有良好生物相容性。另外,相較於市售微脂體對於癌細胞有更佳的傳輸效率,藉由癌症藥物順鉑(diamminedichloroplatinum(II),cisplatin)於乳癌細胞之毒殺
實驗中,聚集碳量子點能以較低劑量之藥物達到更好的療效,同時也能降低藥物所產生的副作用,極具潛力應用於藥物傳遞載體開發。 Cancer nanotherapeutics are rapidly progressing and are being implemented to break through limitations of conventional drug delivery systems. For example, liposomes, spherical vesicles composed of lipid molecules, have been considered as an appropriate drug carriers because of their longer circulation lifetime, which further enhanced the drug accumulation in desired area. However, their high cost, instability and lack of luminescent properties for in vivo tracking are still problematic. Herein, we developed a new drug carrier by assembling highly fluorescent carbon quantum dot into liposome-like structures, which denoted as C-dot aggregates. The half maximal inhibitory concentration (IC50) of C-dot aggregates is 6000 times higher than that of conventional cell-labeling dye, 3,3'-Dioctadecyloxacarbocyanine Perchlorate (DiO), showing excellent biocompatibility. In addition, the high photostability (decrease less than 10 % under the irradiation of Hg lamp(105 W)for 10 hours) and excitation dependent properties of C-dot aggregates indicated it can be applied to long-term fluorescence guiding system. We further applied C-dot aggregates to encapsulate cis-diamminedichloroplatinum(II)(cisplatin), a common chemotherapeutic agent for broad range of cancers. The drug loading efficiency and biocompatibility of C-dot aggregates@cisplatin are comparable with conventional liposomes. Comparing to conventional liposome-based drug delivery system, our system has the advantages of lower cost, low-dosing, high photostability and better delivery efficiency, showing the potential to be used in biological and clinical applications in the future. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59262 |
DOI: | 10.6342/NTU201701366 |
全文授權: | 有償授權 |
顯示於系所單位: | 化學系 |
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