臺灣博碩士論文加值系統

根據衛生福利部2022年統計十大癌症，大腸癌的罹患、死亡人數每年呈現快速增加的趨勢，目前臨床主要治療方式以手術切除為主，但是手術切除往往也會破壞到正常組織，且癌細胞呈現不規則生長，若缺少標靶性治療，效果十分有限。
本研究結合磁熱治療與化學藥物治療，為癌症治療提供新的選擇。以熱分解法合成鐵鉑奈米顆粒( FePt NPs )，並修飾化療藥物氨甲蝶呤(MTX)與SN38，SN38常用於大腸癌治療，MTX具有靶向癌細胞的能力，將修飾上雙藥物的鐵鉑奈米顆粒注射至癌症部位，並施以高週波交替磁場進行磁熱治療。合成的鐵鉑奈米顆粒經由X光繞射分析儀(XRD)與化學能譜儀分析(XPS)鑑定的結果，確認材料由鐵和鉑所組成。利用穿透式電子顯微鏡(TEM)觀察到材料粒徑約為17.56 ± 2.94 nm。藉由傅立葉轉換紅外線光譜儀分析儀(FT-IR)與紫外-可見光分光光度計(UV-Vis)可以確認兩種藥物均成功搭載於鐵鉑奈米顆粒表面。於超導量子干涉磁量儀(SQUID)分析的結果可以確認材料為超順磁性，可用於磁振造影儀(MRI)的造影劑，且可利用高週波將材料加熱而用於癌症熱療。細胞毒性結果可以觀察到，鐵鉑奈米顆粒在濃度250 μg/mL以下時，均有70%以上的細胞存活率。在磁熱細胞治療的結果可以發現細胞存活率被抑制11.56%。
本研究開發之複合奈米顆粒，結合治療及顯影之功能，為癌症治療提供新的策略。

According to the statistics from the Ministry of Health and Welfare in 2022, colorectal cancer has shown a rapid increase in the number of cases and deaths each year. The incidence and mortality rates of colorectal cancer rank second and third, respectively, among all cancers. Currently, the primary clinical treatment method is surgical resection. However, surgery often damages normal tissues, and cancer cells exhibit irregular growth. Without targeted therapy, the effectiveness is limited.
This study combines magnetic hyperthermia therapy with chemotherapy to provide a new option for cancer treatment. Iron-platinum nanoparticles (FePt NPs) were synthesized thermal decomposition method and modified with chemotherapeutic drugs, methotrexate (MTX), and SN38. SN38 is commonly used in the treatment of colorectal cancer, while MTX has the ability to target cancer cells. The dual-drug-modified FePt nanoparticles were injected into the cancer site and subjected to high-frequency alternating magnetic fields for magnetic hyperthermia therapy. The synthesized FePt nanoparticles were confirmed to be composed of iron and platinum through X-ray diffraction analysis (XRD) and X-ray photoelectron spectroscopy (XPS). Transmission electron microscopy (TEM) revealed that the particle size of the material was approximately 17.56 ± 2.94 nm. Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet-visible spectrophotometry (UV-Vis) confirmed the successful loading of both drugs on the surface of the FePt nanoparticles. The results of the superconducting quantum interference device (SQUID) analysis confirmed the material's superparamagnetic properties, making it suitable for use as a contrast agent in magnetic resonance imaging (MRI) and for heating in cancer thermotherapy using high-frequency fields. The cytotoxicity results showed that the FePt nanoparticles had a cell survival rate of over 70% at concentrations below 250 μg/mL. In the results of magnetic hyperthermia cellular therapy, it was observed that the cell viability was suppressed by 11.56%..
The developed composite nanoparticles in this study, combining therapeutic and imaging functions, provide a new strategy for cancer treatment.

摘要 i
ABSTRACT ii
目錄 vi
表目錄 x
圖目錄 xi
第一章 緒論 1
1.1 研究背景與動機 1
1.2 研究目的 2
第二章 文獻回顧 3
2.1 奈米科技與技術 3
2.1.1 奈米材料定義 4
2.1.2 奈米顆粒特性及效應 5
2.2 磁性奈米材料 7
2.2.1 磁性基本原理 7
2.2.2 磁滯曲線(Hysteresis Curve) 8
2.2.3 磁性材料分類 9
2.2.4 磁性奈米顆粒於生醫領域上之應用 12
2.3 鐵鉑奈米顆粒之簡介 14
2.4 氨甲蝶呤(Methotrexate) 16
2.5 SN-38(7-乙基-10-羥基喜樹鹼) 17
2.6 磁熱治療(Magnetic thermal therapy) 18
2.7 大腸癌(Colorectal cancer) 20
2.7.1 大腸癌之簡介 20
2.7.2 大腸癌之診斷方法 22
2.7.3 大腸癌之治療方法 24
第三章 材料與方法 25
3.1 實驗藥品 25
3.2 實驗步驟 26
3.2.1 鐵鉑奈米顆粒合成 26
3.2.2 鐵鉑奈米顆粒表面修飾氨基 27
3.2.3 SN38藥物搭載 27
3.2.4 MTX藥物搭載 27
3.3 實驗架構流程圖 28
3.4 實驗分析儀器 29
3.5 儀器原理介紹 30
3.5.1 X光繞射分析儀(XRD) 30
3.5.2 穿透式電子顯微鏡(TEM) 31
3.5.3 傅立葉傳換紅外光光譜儀(FT-IR) 32
3.5.4 紫外-可見光分光光度計(UV-Vis) 33
3.5.5 超導量子干涉磁量儀(SQUID) 34
3.5.6 高週波電感應加熱器(HF-IHM) 35
3.5.7 電腦斷層掃描(CT) 36
3.5.8 磁振造影儀(MRI) 37
3.6 磁熱升溫測試、藥物搭載及藥物釋放 38
3.6.1 磁熱升溫測試 38
3.6.2 藥物搭載測試 39
3.6.3 藥物釋放測試 39
3.7 細胞實驗(In Vitro Test) 40
3.7.1 細胞培養 40
3.7.2 老鼠纖維母細胞(L929)之生物相容性分析 42
3.7.3 人類大腸癌細胞(SW620)之生物相容性分析 44
3.7.4 人類大腸癌細胞(SW620)對奈米顆粒之內吞效果 45
3.7.5 以ICP-OES測量細胞對奈米顆粒攝取 46
3.7.6 磁加熱對人類大腸癌細胞(SW620)影響 47
3.8 動物實驗(In Vivo Test) 48
3.8.1 磁熱治療 48
第四章 結果與討論 49
4.1 材料之特性分析 49
4.1.1 X光繞射分析(XRD) 49
4.1.2 化學能譜儀分析(XPS) 50
4.1.3 穿透式電子顯微鏡分析(TEM) 52
4.1.4 傅立葉轉換紅外線光譜儀分析(FT-IR) 54
4.1.5 紫外-可見分光光度計(UV-Vis) 55
4.1.6 材料之表面電位(Zeta potential)分析 56
4.2 材料之磁性分析、藥物搭載及藥物釋放 57
4.2.1 SQUID量測 57
4.2.2 材料磁加熱實驗(Magnetic Hyperthermia) 59
4.2.3 磁共振成像(MRI) 60
4.2.4 藥物搭載測試 61
4.2.5 藥物釋放測試 62
4.3 細胞實驗結果(In Vitro Test) 63
4.3.1 材料對老鼠纖維母細胞(L929)之生物相容性測試 63
4.3.2 材料對人類大腸癌細胞(SW620)之生物相容性測試 64
4.3.3 人類大腸癌細胞(SW620)對材料之內吞分析 65
4.3.4 材料之細胞攝取 66
4.3.5 材料對人類大腸癌細胞(SW620)之磁熱治療 67
第五章 結論 69
參考文獻 70

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