請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74835
標題: | 金奈米複合殼球載體於癌症光熱治療合併化療之應用 Application of Micelle-Based Gold Nanoshells in Combined Chemo-Photothermal Cancer Therapy |
作者: | Shin-Yu Lee 李欣瑜 |
指導教授: | 謝銘鈞 |
關鍵字: | 金奈米殼球,奈米藥物,化療,藥物傳輸,光熱治療,癌症治療,內視鏡, gold nanoshells,nanomedicine,chemotherapy,drug delivery,photothermal therapy,cancer therapy,endoscope, |
出版年 : | 2019 |
學位: | 博士 |
摘要: | 金奈米顆粒因其優異的生物相容性和特殊的光學特性近年來逐漸被廣泛應用於生醫檢測、診斷及治療等相關研究。藉由表面電漿共振效應,金奈米顆粒能有效地將特定波長光源的電磁波能量轉換為熱能釋出,因而成為重要的癌症光熱治療媒介材料之一。
本研究利用高分子微胞合成金奈米複合殼球,探討以其作為藥物傳輸系統搭載臨床化療藥物的疏水性衍生物所形成的奈米藥物結合光熱治療所產生的癌症治療效果。利用甲基丙烯酸二甲氨乙酯及己內酯單體所合成的兩性高分子在水相中可自組裝形成可包載疏水性化療藥物的奈米微胞,且其表面帶正電、能吸引帶負電的氯酸金離子,加入還原劑反應後可於微胞表面還原生成微小金奈米顆粒晶種並形成包覆奈米微胞的金殼。此金-高分子複合奈米殼球結構能在近紅外光波段有良好的吸收、具有極佳的生物相容性及光熱轉換能力,並且可有效攜載疏水的化療藥物衍生物如喜樹鹼的代謝產物SN-38與鉑類藥物Oxaliplatin的活性代謝成分DACHPt。殼球結構的金殼層可延緩藥物釋放,吸收近紅外光後產生的局部高溫能使載體結構變得不穩定進而釋放搭載的藥物,達到局部控制釋放的效果。藉由加強滲透度與留滯(enhanced permeability and retention)效應,本研究所製備的金奈米複合殼球能提升腫瘤區域的有效藥物濃度,促進化療治療效果。我們也在細胞及動物實驗中驗證,相較於化療或光熱治療等單一療法,利用此金奈米複合殼球同時進行化療合併光熱治療能顯著增強癌細胞毒殺及腫瘤抑制之效果。此外我們也嘗試利用自組裝之小動物內視鏡系統建立原處位直腸癌模式小鼠,以期未來能與光纖雷射併用、利用該原處位小鼠模式,進一步驗證此金奈米複合殼球載體應用於癌症光熱治療合併化療之潛力。 Combination therapy is a novel strategy to improve the therapeutic outcome of conventional cancer treatment. In the present study, the poly[2-(N,N-dimethylamino)ethyl methacrylate]–poly(ε-caprolactone) (PDMA–PCL) micellar template-based gold nanoshells (GNS) is established as a multifunctional nanocarrier for hydrophobic chemotherapeutic compounds: one is 7-ethyl-10-hydroxycamptothecin (SN-38), a highly hydrophobic metabolite derived from irinotecan, and the other is dichloro(1,2-diaminocyclo-hexane)platinum(II) (DACHPt), the active metabolite of oxaliplatin. The GNS not only function as a drug delivery platform but also provide a remarkable photothermal effect, resulting in synergistically combined chemo-photothermal therapy. With the positively charged outstretched hydrophilic PDMA segments, chloroauric anions are attracted to the PDMA-PCL micellar surface and reduced to gold atoms in situ, forming small seeds that nucleate the subsequent growth of gold nanoshells. The GNS possess a broad surface plasmon resonance peak in the near-infrared (NIR) region and excellent photothermal conversion ability, thus, they can promote a temperature increase that is sufficient to ablate tumor cells under NIR laser irradiation. The local temperature increase also destabilizes the micellar and nanoshell structure, leading to a NIR-triggered release of the encapsulated drug. By exploiting the synergistic effects of combined chemo-photothermal therapy, the drug-loaded GNS exhibit significant tumor suppression compared to using single therapy such as chemotherapy or photothermal therapy alone, suggesting that this drug-loaded micellar GNS may be a potential candidate for future cancer therapy. In addition, we also set up a tailor-made small animal endoscopy system and successfully establish an orthotopic colorectal cancer mouse model, which can be involved as a powerful tool to evaluate the potency of the established nanomedicine in further preclinical studies. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74835 |
DOI: | 10.6342/NTU201904267 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學工程學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-108-1.pdf 目前未授權公開取用 | 4.04 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。