| 研究生: |
曾晧瑜 Tseng, Hao-Yu |
|---|---|
| 論文名稱: |
使用超順磁氧化鐵於癌症高溫治療之研究 Cancer Thermotherapy Using Superparamagnetic Nanoparticles |
| 指導教授: |
李國賓
Lee, Gwo-bin 林錫璋 Lin, Xi-Zhang |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 工程科學系 Department of Engineering Science |
| 論文出版年: | 2007 |
| 畢業學年度: | 95 |
| 語文別: | 中文 |
| 論文頁數: | 95 |
| 中文關鍵詞: | 癌症治療 、高溫療法 、超順磁奈米粒子 、氧化鐵 、高頻交流磁場 |
| 外文關鍵詞: | hyperthermia, superparamagnetic nanoparticles, ferucarbotran, alternating magnetic field, Resovist, Cancer therapy |
| 相關次數: | 點閱:114 下載:2 |
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本研究將超順磁氧化鐵均勻的注射到腫瘤中,並使用交流的磁場加熱超順磁氧化鐵連帶的成功殺死癌細胞並消除腫瘤,且減少傷害正常組織的生長,此種療法屬於所謂的高溫療法(Hyperthermia),所使用的超順磁氧化鐵為可以注射到人體的磁振造影造影劑”Resovist”。體外實驗的部分驗證了該種的超順磁氧化鐵在交流磁場下具備殺死癌細胞的溫度,動物實驗則使用多種方法抑制和消除腫瘤。
本研究設計了一個溫度回饋系統,可以準確的利用交流磁場快速的加熱超順磁氧化鐵到固定的溫度,且溫度變異小於0.2oC,利用該溫度回饋系統加熱本研究中所使用的CT-26直腸癌細胞到37、40、42、 45、 46、47oC探討各個溫度點對於該細胞的影響以及發現當該細胞被加熱到45oC時可以確實殺死該種癌細胞。
動物實驗則成功的局部加熱大鼠鼠肝到59.5 oC,且沒有涵蓋超順磁氧化鐵的部位溫度為37 oC,驗證了使用超順磁氧化鐵局部加熱的可能性。最後使用了多種方法注射超順磁氧化鐵到種有CT-26癌細胞的小鼠腫瘤上,從初期的些微抑制,到中期使用濃縮超順磁氧化鐵大幅的抑制腫瘤生長,最後使用擠壓式幫浦以低流速均勻注射超順磁氧化鐵到腫瘤中成功消除腫瘤,驗證本療法的可行性。
研究目標除了殺死癌細胞消除腫瘤外,目的是將此療法順利應用到臨床醫學上,所使用的藥品皆為可注射到人體身上。所以可以預期的是由於本療法具備局部治療的優點,如果本療法運用在臨床上,病人在治療過程中可以減輕痛苦減少副作用,本新式療法在於治療惡性腫瘤上具有極大的潛力。
[Background and Aims] Cancer is still a major threat to our people and its therapy needs further improvement. Magnetic nanoparticles induced hyperthermia offers a new hope for these patients. We conducted in vitro and in vivo experiments to assess the feasibility of this new form of thermotherapy. [Material and Methods] FDA approved contrast medium for magnetic resonance imaging—ferucarbotran (Resovist○R), was used in our experiments. We set up an instrument which can generate high-frequency magnetic field to induce a localized temperature increase induced by injecting ferucarbotran to the tumors. A feedback temperature control system was successfully developed to keep the nanoparticles at a constant temperature to prevent overheating the targeted cells or animal tumors. For in vitro tests, the relationship between temperature rise and cell survival rate was first investigated. For in vivo tests, murine colon cancer cells were inoculated to the mice. The tumor bearing mice were treated with nanoparticles (resovist) injection and receiving alternating magnetic field induced thermotherapy. Tumor size and survival were observed and recorded. In addition, we did experiments on rodent liver tumors. [Results] By using the feedback temperature control system, superparamagnetic nanoparticles could be heated up to specific temperatures, 37, 40, 42, 45, 46 and 47 oC, respectively, with a variation less than 0.2 oC. With this approach, we found the survival rate of cancer cells would be greatly reduced while CT-26 colon cancer cells were heated above 45oC. Besides, temperatures increase up to 59.5oC can be successfully generated in rodent livers. In-vivo tests also indicated that hyperthermia cancer therapy using this approach could significantly suppress the tumor growth; moreover, complete regression of tumor was achieved by improving our injection technique. The treated animals are free from cancer for a prolonged observation period (90 days). [Discussion] Magnetic nanoparticles induced hyperthermia is very promising to treat cancer successfully. Our system can generate enough heat to kill cancer cells and feedback control device can prevent the possible unwanted side effects. Our studies can provide evidences for further clinical trials.
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