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系統識別號 U0026-1212201211025400
論文名稱(中文) 含有磁性奈米粒子之電紡絲幾丁聚醣奈米纖維應用在癌症之溫熱療法
論文名稱(英文) Electrospun Chitosan Nanofibers Containing Magnetic Nanoparticles for Hyperthermia in Cancer Therapy
校院名稱 成功大學
系所名稱(中) 化學工程學系碩博士班
系所名稱(英) Department of Chemical Engineering
學年度 101
學期 1
出版年 101
研究生(中文) 林大鈞
研究生(英文) Ta-Chun Lin
學號 n38941216
學位類別 博士
語文別 中文
論文頁數 55頁
口試委員 指導教授-林睿哲
口試委員-陳志勇
口試委員-陳炳宏
口試委員-戴政祺
口試委員-林峰輝
口試委員-蔡偉博
口試委員-郭士民
中文關鍵字 幾丁聚醣  亞胺二乙酸  磁性奈米纖維  磁性奈米粒子  超順磁性  電紡絲  奈米纖維  溫熱療法  癌症治療 
英文關鍵字 Cancer therapy  hyperthermia  magnetic nanoparticles  electrospinning  magnetic electrospun nanofibers matrix  chitosan 
學科別分類
中文摘要 對於癌症治療最常使用的方式為外科手術、放射線和藥物治療,這些方式在進行治療過程中,會對身體造成某種程度上的傷害。癌細胞比一般正常細胞具熱敏感性,有一種物理性的癌症治療,可以藉由熱的方式傷害癌細胞使其凋亡,此為溫熱療法(hyperthermia)。磁性奈米粒子(magnetic nanoparticles)具有超順磁性(superparamagnetism),置於高頻變動磁場下(alternative magnetic field, AMF)會產生熱能,利用這種特性可以將磁性奈米粒子應用於癌症治療中的溫熱療法。近期許多研究是將磁性奈米顆粒製作成藥物的方式,然後注入生物體內作癌症溫熱治療。這種含有磁性奈米顆粒的流體注入生物體內後,是否集中並穩定存在於治療部位,目前仍未知數。因此本研究希望製作出一個具磁性的載體(magnetic matrix),藉由外科手術或內視鏡的方式將此載體植入體內,並且能夠集中且穩定存在於治療部位以進行癌症溫熱治療。
本研究設計一種磁性載體以不同的方式將磁性奈米顆粒導入電紡絲中。磁性奈米纖維E-CHS-Fe3O4是將幾丁聚醣製作成電紡絲,然後浸入磁性顆粒溶液中,而磁性顆粒會被嵌在電紡絲網膜中。E-CHS-Fe2+是利用幾丁聚醣具有螯合過渡金屬的特性,先將電紡絲浸入溶液中吸附鐵離子,然後以化學共沈澱法(chemical co-precipitation)反應形成磁性顆粒。亞胺二乙酸(iminodiacetic acid)是一般常見金屬螯合樹脂,在幾丁聚醣的胺基接上亞胺二乙酸,可藉此有效的將金屬離子固定。因此將改質後的幾丁聚醣製作成電紡絲,並利用化學共沈澱法的方式形成磁性奈米纖維E-IDA-Mag。將製作成的磁性奈米纖維放置於變動磁場下(AMF)使其升溫,並評估對細胞的影響。並進一步探討磁性奈米纖維應用在癌症治療中溫熱療法的可行性。
英文摘要 Hyperthermia has been reported as one of the effective cancer treatment modalities since the tumor cells are more temperature sensitive than their normal counterparts. Magnetic nanoparticles were the thermoseeds under an alternating magnetic field and can be used to produce highly localized hyperthermia effect on deep-seated tumor. Nevertheless, effective and precisive delivery of nanoparticles to the treatment-intended site remains a challenge. In this study, Fe3O4 nanoparticles were incorporated onto the crosslinked electrospun chitosan nanofibers using chemical co-precipitation from the Fe ions adsorbed. Such magnetic nanoparticle nanofiber composites could be delivered to the treatment site precisely by surgical or endoscopic method. In this preliminary investigation we have explored various characteristics of the biodegradable electrospun chitosan nanofibers containing magnetic nanoparticles that were prepared by different methods. These methods including (1) E-CHS-Fe3O4: the electrospun chitosan nanofibers immersed directly into magnetic nanoparticle solution; (2) E-CHS-Fe2+: the electrospun chitosan nanofibers immersed into Fe+2/Fe+3 solution initially then followed by chemical co-precipitation for magnetic nanoparticles.
Iminodiacetic acid (IDA) functionality was grafted onto the chitosan with an aim to increase the amount of magnetic nanoparticles formed in the electrospun magnetic nanofiber composite. The morphology, crystalline phase as well as the magnetism characteristic of the magnetic electrospun nanofiber matrixes was analyzed. The heating properties of these magnetic electrospun nanofibers matrixes under an alternating magnetic field (AMF) were investigated under a frequency of 750 kHz and magnetic intensity of 0.8T. In vitro cell incubation experiments indicated that these magnetic electrospun nanofibers matrixes can effectively reduced the tumor cell proliferation under the application of magnetic field. This finding suggested the magnetic electrospun chitosan nanofiber composite can be of potential for hyperthermia treatment.
論文目次 摘要 I
Abstract III
誌謝 V
目錄 VI
圖目錄 VIII
附錄 IX
第 1 章 文獻回顧 1
1.1 癌症的形成 1
1.2 癌症治療 2
1.3 溫熱療法 3
1.4 磁性奈米顆粒 5
1.5 人體防禦系統 6
1.6 磁性奈米顆粒在生物醫學的應用 8
1.7 電紡絲 9
1.8 磁性奈米纖維 10
1.9 幾丁聚醣 11
1.10 研究動機 13
第 2 章 實驗 15
2.1 實驗藥品 16
2.2 實驗儀器 17
2.3 實驗方法 18
2.3.1 亞胺二乙酸活化 (ECH-IDA) 18
2.3.2 幾丁聚醣改質 (CTS-IDA) 18
2.3.3 電紡絲溶液的製備 18
2.3.4 電紡絲的製作 19
2.3.5 電紡絲的交聯固定(crosslink) 19
2.3.6 磁性氧化鐵奈米顆粒(Fe3O4 nanoparticles)的製備 19
2.3.7 電紡絲吸附磁性氧化鐵的實驗 20
2.3.8 磁性奈米纖維的命名 20
2.3.9 磁性奈米纖維的分析 20
2.3.10 磁性奈米纖維加熱實驗 21
2.3.11 細胞毒性測試 21
2.3.12 細胞加熱實驗 22
第 3 章 結果 23
3.1 幾丁聚醣改質(CTS-IDA) 23
3.2 電紡絲的製作 23
3.3 電紡絲的交聯固定 24
3.4 磁性奈米纖維的製作 26
3.5 磁性奈米纖維的分析 27
3.6 細胞實驗 28
第 4 章 討論 30
第 5 章 結論 33
參考文獻 34
附錄 46
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