( 您好!臺灣時間:2021/02/27 01:02
字體大小: 字級放大   字級縮小   預設字形  


研究生(外文):Shu-Wei Liu
論文名稱(外文):Enhanced Photothermal Therapy Using Gold Nanodroplets
指導教授(外文):Pai-Chi Li
口試委員(外文):Chih-Kuang YehChe-Chou ShenHuan-Cheng ChangChun-Yen Lai
外文關鍵詞:photothermal therapygold nanodropletlaser and ultrasound
  • 被引用被引用:0
  • 點閱點閱:421
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0

Photothermal therapy refers to the use of heating from electromagnetic radiation to treat various medical conditions, including cancer. For example, researchers have been using targeting gold nanoparticles to specific tumor sites as a therapeutic agent with the application of near infrared laser irradiation to induce heating and concomitant tumor cell necrosis. Comparing to other technologies, photothermal therapy can be highly effective with low side effects. It becomes clear that the quantity of gold nanoparticles that can be delivered and accumulated in the tumor is a key factor determining the therapeutic efficacy as well as an important research subject. One of the common approaches to enhancing delivery of the therapeutic agent is to employ micro bubbles as a carrier. Nonetheless, these microbubbles are generally not stable. Therefore, the hypothesis of this study is that by using nanodroplets as the carrier, the stability can be improved and thus the delivery can be enhanced. Moreover, we further hypothesize that by combining laser and ultrasound, liquid-to-gas phase change can be effectively induced and the subsequent bubble destruction can improve the cavitational effects and thus the delivery of therapeutic agent. To test these hypotheses, in vitro and in vivo experiments were conducted in this study. First, the in house therapeutic agents were characterized. Second, the inertial cavitation does was measured under various conditions to quantitatively represent the amount of the cavitational effects. Third, the delivery efficiency of gold nanoparticles between microbubbles and nanodroplets was compared. Finally, cell toxicity tests and animal experiments were conducted to evaluate photothermal therapeutic effects. Results show that the combination of laser with ultrasound provides stronger cavitational effects and synergistic treatment efficacy. Specifically, the destruction ratio of gold nanodroplets using both laser and ultrasound is approximately 45% and the optical density value representing the amount of gold delivered into the cells is 0.027, both are higher than those from gold microbubbles. Furthermore, the cell viability under both laser and ultrasound is 42%, which is also the lowest among all the treatment strategies that were included in this study. It is concluded that the use of gold nanodroplets and the combination of laser and ultrasound does have the potential to be an effective technology for plasmonic phothermal therapy.

口試委員審定書 I
致謝 II
中文摘要 III
Abstract IV
目錄 VI
圖目錄 IX
表目錄 XI
第一章 緒論 1
1.1 癌症與光熱治療 1
1.2 超音波對比劑 4
1.3 穴蝕效應及其治療上的應用 7
1.4 研究動機與目標 9
1.5 論文架構 11
第二章 實驗材料與方法 12
2.1 對比劑製作 12
2.1.1 實驗架構及流程 12
2.1.2 氣化現象偵測 13
2.1.3離心篩選測試 14
2.1.4 升溫現象偵測 14
2.2 氣化與穴蝕效應實驗 14
2.2.1 實驗架構及流程 14
2.2.2 氣化效應之誘發與偵測 17
2.2.3穴蝕效應之誘發與偵測 17
2.3 奈米粒子釋放效率實驗 21
2.3.1 對比劑配置 21
2.3.2 實驗架構及流程 21
2.3.3 破裂比例評估法 22
2.3.4 吸光值評估法 23
2.4 光熱治療實驗 23
2.4.1細胞實驗 23
2.4.2 小動物實驗 26
第三章 實驗結果 28
3.1 奈米金液滴製作及特性評估 28
3.1.1 粒徑及濃度 28
3.1.2 氣化能力 29
3.1.3 離心分析 30
3.1.4 升溫效率評估 32
3.2 雷射輔助奈米金液滴氣化與穴蝕效應 33
3.2.1 B-mode影像觀察 33
3.2.2 粒徑濃度分析 35
3.2.3 聲壓 vs dICD 37
3.2.5 雷射強度 vs dICD 39
3.2.6 濃度 vs dICD 40
3.3奈米金粒子釋放效率實驗 41
3.3.1 破裂比例評估法 41
3.3.2 吸光值評估法 43
3.4光熱治療實驗 45
3.4.1 細胞毒性實驗 45
3.4.2 小動物治療實驗 46
第四章 分析與討論 48
4.1 雷射輔助超音波奈米金液滴穴蝕效應之特性探討 48
4.2奈米金粒子釋放效率之結果探討 50
4.3光熱治療效果探討 52
第五章 結論與未來工作 56
第六章 參考文獻 59

Ferlay, J., et al., Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 2010. 127(12): p. 2893-917.
2.Knudson, A.G., Mutation and cancer: statistical study of retinoblastoma. Proceedings of the National Academy of Sciences, 1971. 68(4): p. 820-823.
3.Fisher, B., et al., Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. New England Journal of Medicine, 2002. 347(16): p. 1233-1241.
4.Sekine, I., et al., A literature review of molecular markers predictive of clinical response to cytotoxic chemotherapy in patients with breast cancer. Int J Clin Oncol, 2009. 14(2): p. 112-9.
5.Zelefsky, M.J., et al., High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. International Journal of Radiation Oncology* Biology* Physics, 2002. 53(5): p. 1111-1116.
6.Eramo, A., et al., Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ, 2006. 13(7): p. 1238-41.
7.Schulz-Ertner, D. and H. Tsujii, Particle radiation therapy using proton and heavier ion beams. J Clin Oncol, 2007. 25(8): p. 953-64.
8.COLEY, W.B., The Classic: The Treatment of Malignant Tumors by Repeated Inoculations of Erysipelas: With a Report of Ten Original Cases. Clinical orthopaedics and related research, 1991. 262: p. 3-11.
9.Bickels, J., et al., Coley''s toxin: historical perspective. Isr Med Assoc J, 2002. 4(6): p. 471-2.
10.Skinner, M.G., et al., A theoretical comparison of energy sources-microwave, ultrasound and laser-for interstitial thermal therapy. Physics in Medicine and Biology, 1998. 43(12): p. 3535.
11.Han, B., et al., Development of quantum dot-mediated fluorescence thermometry for thermal therapies. Ann Biomed Eng, 2009. 37(6): p. 1230-9.
12.Brunetaud, J., et al., Non-PDT uses of lasers in oncology. Lasers in medical science, 1995. 10(1): p. 3-8.
13.Oldenburg, S., et al., Nanoengineering of optical resonances. Chemical Physics Letters, 1998. 288(2): p. 243-247.
14.Pitsillides, C.M., et al., Selective cell targeting with light-absorbing microparticles and nanoparticles. Biophysical journal, 2003. 84(6): p. 4023-4032.
15.Huang, X., et al., Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. Journal of the American Chemical Society, 2006. 128(6): p. 2115-2120.
16.Ghosh, P., et al., Gold nanoparticles in delivery applications. Adv Drug Deliv Rev, 2008. 60(11): p. 1307-15.
17.Gramiak, R. and P.M. Shah, Echocardiography of the aortic root. Investigative radiology, 1968. 3(5): p. 356-366.
18.Goldberg, B.B., J.-B. Liu, and F. Forsberg, Ultrasound contrast agents: a review. Ultrasound in medicine &; biology, 1994. 20(4): p. 319-333.
19.Sirsi, S. and M. Borden, Microbubble Compositions, Properties and Biomedical Applications. Bubble Sci Eng Technol, 2009. 1(1-2): p. 3-17.
20.Lawrence, M.J. and G.D. Rees, Microemulsion-based media as novel drug delivery systems. Advanced drug delivery reviews, 2000. 45(1): p. 89-121.
21.Cui, W., et al., Preparation and evaluation of poly (L&;#8208;lactide&;#8208;co&;#8208;glycolide)(PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2005. 73(1): p. 171-178.
22.Faez, T., et al., 20 years of ultrasound contrast agent modeling. IEEE Trans Ultrason Ferroelectr Freq Control, 2013. 60(1): p. 7-20.
23.Lum, A.F., et al., Ultrasound radiation force enables targeted deposition of model drug carriers loaded on microbubbles. J Control Release, 2006. 111(1-2): p. 128-34.
24.Wang, Y.H., et al., Photoacoustic/ultrasound dual-modality contrast agent and its application to thermotherapy. J Biomed Opt, 2012. 17(4): p. 045001.
25.Sheeran, P.S., et al., Toward ultrasound molecular imaging with phase-change contrast agents: an in vitro proof of principle. Ultrasound Med Biol, 2013. 39(5): p. 893-902.
26.Apfel, R.E., Tensile strength of superheated n-hexane droplets. Nature, 1971. 233(41): p. 119-121.
27.Kripfgans, O.D., et al., Acoustic droplet vaporization for therapeutic and diagnostic applications. Ultrasound in medicine &; biology, 2000. 26(7): p. 1177-1189.
28.Sheeran, P.S., et al., Design of ultrasonically-activatable nanoparticles using low boiling point perfluorocarbons. Biomaterials, 2012. 33(11): p. 3262-9.
29.Rapoport, N.Y., et al., Microbubble generation in phase-shift nanoemulsions used as anticancer drug carriers. Bubble Science, Engineering &; Technology, 2009. 1(1-2): p. 31-39.
30.Kheirolomoom, A., et al., Acoustically-active microbubbles conjugated to liposomes: characterization of a proposed drug delivery vehicle. Journal of Controlled Release, 2007. 118(3): p. 275-284.
31.Fabiilli, M.L., et al., Delivery of water-soluble drugs using acoustically triggered perfluorocarbon double emulsions. Pharmaceutical research, 2010. 27(12): p. 2753-2765.
32.Wilson, K., K. Homan, and S. Emelianov, Biomedical photoacoustics beyond thermal expansion using triggered nanodroplet vaporization for contrast-enhanced imaging. Nat Commun, 2012. 3: p. 618.
33.Burns, P.N. and S.R. Wilson, Microbubble contrast for radiological imaging: 1. Principles. Ultrasound quarterly, 2006. 22(1): p. 5-13.
34.Leighton, T., The acoustic bubble. 1994: Academic press.
35.Xu, S., et al. Cavitation enhanced ultrasound thrombolysis. in Ultrasonics Symposium, 2008. IUS 2008. IEEE. 2008. IEEE.
36.Plesset, M. and T. Mitchell, On the stability of the spherical shape of a vapor cavity in a liquid. Quarterly of Applied Mathematics, 1956. 13: p. 419-430.
37.FDA, Information for Manufacturers Seeking Marketing Clearance of Diagnostic Ultrasound Systems and Transducers. 2008: p. 10-21.
38.Newman, C.M., et al., Ultrasound gene therapy: on the road from concept to reality. Echocardiography, 2001. 18(4): p. 339-347.
39.Mitragotri, S., Healing sound: the use of ultrasound in drug delivery and other therapeutic applications. Nature Reviews Drug Discovery, 2005. 4(3): p. 255-260.
40.Wang, C.H., et al., Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis. Biomaterials, 2012. 33(6): p. 1939-47.
41.Wray, W.O., T. Aida, and R.B. Dyer, Photoacoustic cavitation and heat transfer effects in the laser-induced temperature jump in water. Applied Physics B: Lasers and Optics, 2002. 74(1): p. 57-66.
42.Ju, H., R.A. Roy, and T.W. Murray, Gold nanoparticle targeted photoacoustic cavitation for potential deep tissue imaging and therapy. Biomedical optics express, 2013. 4(1): p. 66-76.
43.Moon, H.K., S.H. Lee, and H.C. Choi, In vivo near-infrared mediated tumor destruction by photothermal effect of carbon nanotubes. Acs Nano, 2009. 3(11): p. 3707-3713.
44.Brayman, A.A., et al., Hemolysis of 40% hematocrit, Albunex< sup>R-supplemented human erythrocytes by pulsed ultrasound: Frequency, acoustic pressure and pulse length dependence. Ultrasound in medicine &; biology, 1997. 23(8): p. 1237-1250.
45.Chen, W.-S., et al., The pulse length-dependence of inertial cavitation dose and hemolysis. Ultrasound in medicine &; biology, 2003. 29(5): p. 739-748.
46.Scholle, K., et al., 2 μm laser sources and their possible applications. 2010.
47.Farny, C.H., et al., Nucleating cavitation from laser-illuminated nano-particles. Acoustics Research Letters Online, 2005. 6(3): p. 138-143.
48.Rigopoulos, A.G., et al., Echocardiography-guided percutaneous septal ablation in patients with hypertrophic obstructive cardiomyopathy: one year follow-up. Hellenic J cardiol, 2003. 44: p. 171-179.
49.Dein, F.J., et al., Avian leucocyte counting using the hemocytometer. Journal of Zoo and Wildlife Medicine, 1994: p. 432-437.
50.Giesecke, T. and K. Hynynen, Ultrasound-mediated cavitation thresholds of liquid perfluorocarbon droplets in vitro. Ultrasound in Medicine &; Biology, 2003. 29(9): p. 1359-1365.
51.Matsunaga, T.O., et al., Phase-change nanoparticles using highly volatile perfluorocarbons: toward a platform for extravascular ultrasound imaging. Theranostics, 2012. 2(12): p. 1185-98.
52.Zhang, P. and T. Porter, An in vitro study of a phase-shift nanoemulsion: a potential nucleation agent for bubble-enhanced HIFU tumor ablation. Ultrasound Med Biol, 2010. 36(11): p. 1856-66.
53.Atri, M., et al., Contrast-enhanced ultrasonography for real-time monitoring of interstitial laser thermal therapy in the focal treatment of prostate cancer. Canadian Urological Association Journal, 2009. 3(2): p. 125.
54.Zhang, M., et al., Initial investigation of acoustic droplet vaporization for occlusion in canine kidney. Ultrasound Med Biol, 2010. 36(10): p. 1691-703.
55.Hall, C.S., et al., Experimental determination of phase velocity of perfluorocarbons: applications to targeted contrast agents. Ultrasonics, Ferroelectrics and Frequency Control, IEEE Transactions on, 2000. 47(1): p. 75-84.
56.Oraevsky, A.A., et al., Enhanced delivery of gold nanoparticles by acoustic cavitation for photoacoustic imaging and photothermal therapy. 2013. 8581: p. 858123.
57.Huang, X. and M.A. El-Sayed, Plasmonic photo-thermal therapy (PPTT). Alexandria Journal of Medicine, 2011. 47(1): p. 1-9.
58.Sheeran, P.S., et al., Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound. Langmuir, 2011. 27(17): p. 10412-20.
59.McLaughlan, J.R., et al., Ultrasonic enhancement of photoacoustic emissions by

第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔