奈米抗癌藥物結合脈衝超音波及微氣泡與熱治療在小鼠耳朵腫瘤之研究

Nanodrug Combined with Physical Methods for Cancer Tumor Treatment in A Mouse Ear Model

許恆瑞(Heng-Ruei Shiu)

指導教授 ： 林文澧

國立臺灣大學/工學院/醫學工程學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.00236

摘要

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。

關鍵字

超音波 ； 微氣泡 ； 熱治療 ； 藥物傳遞 ； 小鼠耳朵腫瘤模型

並列摘要

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.

並列關鍵字

ultrasound ； microbubbles ； hyperthermia ； drug delivery ； mouse ear tumor model

參考文獻

2. Sboros,V.(2008). "Response of contrast agents to ultrasound." Advanced Drug Delivery Reviews 60(10): 1117-1136.

3. Frenkel,V.(2008). "Ultrasound mediated delivery of drugs and genes to solid tumors." Advanced Drug Delivery Reviews 60(10): 1193-1208.

4. Pitt,WG., Husseini,GA.,and Staples,BJ.(2004). "Ultrasonic drug delivery – a general review. " Expert Opin Drug Deliv 1(1): 37–56.

5. Husseini,GA., and Pitt,WG.(2008). "The use of ultrasound and micelles in cancer treatment. " J Nanosci Nanotechnol 8(5): 2205–2215.

6. Ferrara,KW.(2008). "Driving delivery vehicles with ultrasound." Advanced Drug Delivery Reviews 60(10): 1097-1102.