臺灣博碩士論文加值系統

近年來有研究指出，藥物搭配超音波與微氣泡和藥物搭配熱治療兩者治療腫瘤的方式皆能強化藥物傳遞，進而增加藥物在腫瘤內的濃度，使腫瘤得到較好的治療效果。而本研究利用小鼠耳朵腫瘤模型(Mouse Ear Tumor Model)，使用奈米藥物Doxil、超音波與微氣泡及43℃加熱15分鐘之熱治療三種治療方式互相做搭配，探討在治療腫瘤的情形，總共治療八次，每兩天治療一次，治療前四次後，休息一個星期之後，再持續給予後四次的治療。研究結果觀察到真正對腫瘤治療比較有效的是奈米藥物Doxil搭配上超音波及微氣泡、奈米藥物Doxil搭配上43℃加熱15分鐘之熱治療、奈米藥物Doxil搭配上超音波及微氣泡又加再加上43℃加熱15分鐘之熱治療這三組；而以腫瘤生長狀態而言，又以奈米藥物Doxil搭配上超音波及微氣泡再加上43℃加熱15分鐘之熱治療和奈米藥物Doxil搭配上43℃加熱15分鐘之熱治療這兩組較有效，而奈米藥物Doxil搭配上超音波及微氣泡再加上43℃加熱15分鐘之熱治療甚至能使腫瘤逐漸變小到幾乎看不見，在小腫瘤的治療上有相當顯著的治療效果。

Studies show that ultrasound (US) with microbubbles (MB) or hyperthermia (HT) could enhance the delivery of nanoparticles into tumor tissues. In this research, we used mouse ear tumor model to study the effectiveness of nanodrug on the tumor treatment with the enhancement of ultrasound/ microbubbles and/or hyperthermia, and observed the tumor growth with microscopy. The treatment procedure was arranged with four successive treatments every other day, and then followed the same four successive treatments after a week off.Experimental results showed that treatment enhancement can be observed for nanodrug injection followed by MB/US, or HT (43℃, 15 min),or MB/US/HT. The treatment set with MB/US/HT following nanodrug injection can even make the tumor disappear. The results of this study indicates that MB/US/HT following the injection of nanodrug is a very promising method for effective tumor treatment.

誌謝…………………………………………………………………………………....I
摘要…………………………………………………………………………………..II
Abstract……………………………………………………………….....III
目錄…………………………………………………………………………………..IV
圖目錄………………………………………………………………………………...V
第一章 緒論…………………………………………………………………….......1
1-1 超音波……………………………………………………………………..1
1-2 空蝕化效應………………………………………………………………..1
1-3 熱效應……………………………………………………………………..2
1-4 超音波加強藥物傳遞的機制……………………………………………..3
1-5 熱治療……………………………………………………………………..3
1-6 奈米抗癌藥物Doxil……………………………………………………....5
1-7 研究目的…………………………………………………………………..5
第二章 實驗設備與材料方法……………………………………………………...8
2-1 腫瘤細胞株………………………………………………………………..9
2-2 實驗動物…………………………………………………………………..9
2-3 抗癌藥……………………………………………………………………..9
2-4 超音波顯影劑……………………………………………………………..9
2-5 超音波設備………………………………………………………………10
2-6 超音波參數………………………………………………………………10
2-7 加熱系統…………………………………………………………………10
2-8 顯微鏡系統………………………………………………………………11
2-9 顯微鏡影像………………………………………………………………11
2-10數值分析方法…………………………………………………………….11
2-11 實驗設計與流程…………………………………………………………12
第三章 結果……………………………………………………………………….16
第四章 討論……………………………………………………………………….60
第五章 結論與未來工作………………………………………………………….63
參考文獻……………………………………………………………………………..64
圖目錄
圖1.1 慣性空蝕化的閥值…………………………………………………………..6
圖1.2 慣性空蝕化的現象示意圖………………………………………………......7
圖1.3 超音波強化藥物傳送示意圖………………………………………………..7
圖1.4 熱治療強化藥物傳送的示意圖……………………………………………..8
圖2.1 超音波設備…………………………………………………………………13
圖2.2 超音波能量分布圖…………………………………………………………13
圖2.3 加熱系統……………………………………………………………………14
圖2.4 螢光解剖顯微鏡……………………………………………………………14
圖2.5 顯微鏡影像…………………………………………………………………15
圖2.6 實驗流程圖…………………………………………………………………15
圖3.1 Control組在顯微鏡下觀察到的影像……………………………………..16
圖3.2 Control組在顯微鏡下觀察到的影像……………………………………...17
圖3.3 Control組在顯微鏡下觀察到的影像……………………………………...18
圖3.4 Doxil組在顯微鏡下觀察到的影像………………………………………...20
圖3.5 Doxil組在顯微鏡下觀察到的影像………………………………………..21
圖3.6 Doxil組在顯微鏡下觀察到的影像………………………………………..22
圖3.7 Doxil_MB US組在顯微鏡下觀察到的影像………………………………24
圖3.8 Doxil_MB US組在顯微鏡下觀察到的影像………………………………25
圖3.9 Doxil_MB US組在顯微鏡下觀察到的影像………………………………26
圖3.10 Doxil_MB US組在顯微鏡下觀察到的影像……………………………..27
圖3.11 HT組在顯微鏡下觀察到的影像…………………………………………29
圖3.12 HT組在顯微鏡下觀察到的影像…………………………………………30
圖3.13 HT組在顯微鏡下觀察到的影像…………………………………………31
圖3.14 Doxil_HT組在顯微鏡下觀察到的影像………………………………….33
圖3.15 Doxil_HT組在顯微鏡下觀察到的影像………………………………….34
圖3.16 Doxil_HT組在顯微鏡下觀察到的影像………………………………….35
圖3.17 Doxil_HT組在顯微鏡下觀察到的影像………………………………….36
圖3.18 Doxil_MB US_HT組在顯微鏡下觀察到的影像………………………..38
圖3.19 Doxil_MB US_HT組在顯微鏡下觀察到的影像………………………..39
圖3.20 Doxil_MB US_HT組在顯微鏡下觀察到的影像………………………..40
圖3.21 Doxil_MB US_HT組在顯微鏡下觀察到的影像………………………..41
圖3.22 Doxil_MB US_HT組在顯微鏡下觀察到的影像………………………..42
圖3.23 六組間治療前後的比較…………………………………………………..44
圖3.24 六組間治療前後的比較…………………………………………………..46
圖3.25 六組間治療前後的比較…………………………………………………..48
圖3.26 HT組、Doxil_HT組、Doxil_MB US_HT組的腫瘤體積大小與時間之關係圖………………………………………………………………………………..50
圖3.27 HT組、Doxil_HT組、Doxil_MB US_HT組的腫瘤體積成長百分比與時間之關係圖………………………………………………………………………..51
圖3.28 Doxil組、Doxil_MB US組、Doxil_HT組、Doxil_MB US_HT組的腫瘤體積大小與時間之關係圖………………………………………………………..52
圖3.29 Doxil組、Doxil_MB US組、Doxil_HT組、Doxil_MB US_HT組的腫瘤體積成長百分比與時間之關係圖………………………………………………..53


圖3.30 Doxil_MB US組、Doxil_HT組、Doxil_MB US_HT組的腫瘤體積大小與時間之關係圖……………………………………………………………………..54
圖3.31 Doxil_MB US組、Doxil_HT組、Doxil_MB US_HT組的腫瘤體積成長百分比與時間之關係圖……………………………………………………………..55
圖3.32 Control組、HT組、Doxil組、Doxil_MB US組、Doxil_ HT組、Doxil_MB US_HT組的腫瘤體積大小與時間之關係圖………………………………………56
圖3.33 Control組、HT組、Doxil組、Doxil_MB US組、Doxil_ HT組、Doxil_MB US_HT組的腫瘤體積大小取Log與時間之semiLog關係圖……………………57
圖3.34 Control組、HT組、Doxil組、Doxil_MB US組、Doxil_ HT組、Doxil_MB US_HT組的腫瘤體積成長百分比取Log與時間之semiLog關係圖……………58

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