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研究生: 邱崙捷
Chiu, Lun-Chieh
論文名稱: 磁性奈米顆粒結合抗癌藥Doxorubicin之體內及體外抗腫瘤實驗
The in vivo and in vitro Anti-tumor Study of Magnetic Nano-Particles Coated with Anti-tumor Drug Doxorubicin
指導教授: 蕭世裕
Shaw, Shyh-Yu
學位類別: 碩士
Master
系所名稱: 生物科學與科技學院 - 生物科技研究所
Institute of Biotechnology
論文出版年: 2004
畢業學年度: 92
語文別: 中文
論文頁數: 56
中文關鍵詞: 磁性奈米抗癌
外文關鍵詞: magnetic nanoparticle, doxorubicin
相關次數: 點閱:58下載:2
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  • 本實驗結合抗癌藥物doxorubicin包覆氧化鐵磁性奈米顆粒,合成三種新型的磁性奈米抗癌藥物。利用磁性的導引可以將此藥物標定到腫瘤部位治療,一方面提高患部藥物的濃度,另一方面可以降低其他部位的藥物濃度,減少副作用。這次實驗之目的是測試新型磁性抗癌藥物的體內及體外活性。
    在體外的活性測試實驗中,我們使用小鼠膀胱癌細胞(MBT-2)利用MTT assay來定量細胞的存活率。我們比較doxorubicin包覆磁性奈米粒子與單純磁性奈米粒子還有單純doxorubicin的活性,發現doxorubicin包覆磁性奈米粒子表現的活性與單純doxorubicin相似,但是單純磁性奈米粒子並沒有毒殺細胞的活性。另外我們利用外加磁場來標定磁性奈米顆粒,發現doxorubicin包覆磁性奈米粒子可以被標定並且毒殺癌細胞。但對於非腫瘤細胞-猴子腎臟細胞COS-7 (monkey, African green, kidney)並沒有明顯毒殺的能力。在體內實驗中我們首先誘導小鼠產生腫瘤,並轉置一個小磁鐵在腫瘤中,接著注射doxorubicin包覆磁性奈米粒子進入小鼠腫瘤中。發現doxorubicin包覆磁性奈米粒子有標定腫瘤位置的效果並毒殺腫瘤細胞。

    In our study, we synthesized magnetic nano-particles coated with an anti-cancer medicine doxorubicin to form three new-types magnetic nano anti-cancer medicine. By magnetic leading, the magnetic nano-particles can be targeted to the tumor site for therapy. The advantages are increasing drug concentration at the tumor and lowering drug concentration in the other region of body to avoid the significant side effect of chemical drugs. Our purpose is examining the in vivo and in vitro activity of this new-type anti-cancer medicine.
    In vitro activity experiment was performed on murine bladder tumor cell (MBT-2) and the survival cell was quantitated by MTT assay. The activity of magnetic nano-particles coated with doxorubicin were compared to free magnetic nano-particles and free doxorubicin. We found that magnetic nano-particle coated with doxorubicin exhibits activity similar to free doxorubicin but the magnetic nano-particle alone dosen’t show any activity. Besides, when we provide a external magnetic field to target the magnetic nano-particles and we found that magnetic nano-particles coated with doxorubicin can be targeted and killed the cancer cell. But there are no observable toxicity in the same test on normal cell line COS-7. In In vivo experiment, we first induced tumor formation in mice, and then implanted a small magnetic in tumor. Then we injected magnetic nano-particles with doxorubicin into the tumor. We found that magnetic nano-particles coated with doxorubicin can be target to the tumor site and kill the tumor cells.

    目錄 中文摘要………………………………………………………Ⅰ 英文摘要………………………………………………………Ⅱ 目錄……………………………………………………………Ⅲ 圖目錄…………………………………………………………Ⅳ 表目錄…………………………………………………………Ⅴ 緒論……………………………………………………………1 材料與方法……………………………………………………7 結果與討論……………………………………………………15 結論……………………………………………………………28 參考文獻………………………………………………………54

    1. Karnofsky, D. A. The use of nitrogen mustards in the palliative treatment of carcinoma. Cancer 1, 634-656, 1948.
    2. Farber, S. Temporary remissionsin acute leukemia in children produced by folic acid antagonist 4-amethophteroylglutamic acid (aminopterin). N. Engl. J. Med. 238, 787-793, 1948.
    3. Bruce C. Baguley, David J. Kerr Anticancer durg development. Academic press. San Diego, California, USA. 2-8, 2002.
    4. Meyn, M. S. Ataxia-telangiectasia and cellular responses to DNA damage. Cancer Res. 55, 5991-6001, 1995.
    5. Pardoll, D. M. Cancer vaccines. Trends Pharmacol. Sci. 14, 202-208, 1993
    6. Folkman, J. Tumor angiogenesis: Therapeutic implocation. N. Engl. J. Med. 285, 1182-1186, 1971.
    7. Zwelling, L. A. Protein-associated DNA strand breaks in L1210 cells treated with the DNA intercalating agents 4’-(9-acridiny-lamino)-methanesulfon-m-anisidide and adeiamycin. Biochemistry 20, 6553-6563, 1981.
    8. Nelson, E. M. Mechanism of antitumor drug action: Poisoning of mammalian topoisomerase on DNA by Ⅱ4’-(9-acridiny-lamino)-methanesulfon-m-anisidide. Proc. Natl. Acad. Sci. USA 81, 1361-1364, 1984.
    9. 廖繼鼎編著臨床腫瘤學合記圖書出版社台灣台北126-131 2003.
    10. W.A.R.Van Heeswijk, Synthesis, characterization and anti-tumor activity of acromolecular prodrugs of adriamycin, in: J.M. Anderson, S.W. Kim (Eds.), Recent Advances in Drug Delivery Systems, Plenum, New York, pp.77–100, 1984.
    11. D.J. Kerr, Microparticulate drug delivery systems as an adjunct to cancer treatment, Cancer Drug Deliv. 4, 55–61, 1987.
    12. C. Jones, M.A. Burton, B.N. Gray, Albumin microspheres as vehicles for the sustained and controlled release of doxorubicin, J. Pharm. Pharmacol. 41, 813–816, 1989.
    13. G.S. Kwon, M. Naito, Y. Masayuki, T. Okano, Y. Sakurai, K. Kataoka, Physical entrapment of adriamycin in AB block copolymer
    54
    micelles, Pharm. Res. 12, 192–195, 1995.
    14. P. Couvreur, L. Roblot-Treupel, M.F. Poupon, F. Brasseur, F. Puisieux, Nanoparticles as microcarriers for anticancer drugs, Adv. Drug Deliv. Rev. 5, 209–230, 1990.
    15. Kevin A. Janes, Marie P. Fresneau , Ana Marazuela , Angels Fabra, Marýa Jose Alonso, Journal of Controlled Release 73, 255–267, 2001.
    16. S. I. Kang, K. Na, Y. H. Bae, Colloids and Surfaces A: Physicochem. Eng. Aspects 231, 103-112, 2003.
    17. H. S. Yoo, K. H. Lee, J. E. Oh, T. G. Park, Journal of Controlled Release 68, 419-431, 2000.
    18. S. Mitra, U. Gaur, P. C. Ghosh, A. N. Maitra, Journal of Controlled Release 74, 317-323, 2001.
    19. S.E. Gelperina, Toxicology Letters 126, 131–141, 2002.
    20. A. Fundaro, R. Cavalli, A. Bargoni, D. Vighetto, G. P. Zara, M. R. Gasco, Pharmacological Research, Vol. 42, No. 4, 337-343, 2000.
    21. J. Kreuter, Advanced Drug Delivery Reviews 47, 65–81, 2001.
    22. R. Gorodetskya, Journal of Controlled Release 95, 477– 488, 2004.
    23. A. Gabizon, R. Shiota, D. Papahadjopoulos, Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times, J. Natl. Cancer Inst. 81, 1484–1488, 1989.
    24. Rom E. Eliaz and Francis C. Szoka, Jr., Cancer Res. 15; 61(6):2592-601, 2001.
    25. International Journal of Clinical Pharmacology and Therapeutics, 40, 8, 387-388, 2002.
    26. G. Batist, G. Ramakrishnan, Journal of Clinical Oncology, 19, 5, 1444-1454, 2001.
    27. C. L. Shapiro, T. Ervin, L. Welles, N. Azarnia, J. Keating, Daniel F. Hayes, Journal of Clinical Oncology, 17, 5, 1435, 1999.
    28. Huczko A, Appl Phys A-Mater Sci Process 70, 365, 2000.
    29. Safa rõÂk I, Safa rõÂkova M , J Chromatogr B 722, 33, 1999.
    30. Safa rõÂk I, J Appl Bacteriol 78, 575, 1995.
    31. Safa rõÂkova M, Magn Electr Sep 10, 223, 2001.
    32. Safa rõÂk I, Zborowski M (eds) Scientific and Clinical Applications of Magnetic Carriers. Plenum, New York London, p 323, 1997.
    33. Ivo Safarik, Mirka Safarikova, Monatshefte fur Chemie 133,
    55
    56737-759, 2002.
    34. Lubbe AS, Bergemann C, In: Hafeli U, Schutt W, Teller J, Zborowski M (eds) Scientifc and Clinical Applications of Magnetic Carriers. Plenum, New York London, 457, 1997
    35. Widder KJ, Senyei AE, Pharmacol Therapeut 20, 377, 1983.
    36. Torchilin VP, Eur J Pharm Sci 11, S81, 2000.
    37. Orekhova NM, Akchurin RS, Thromb Res 57, 611, 1990.
    38. Andreas Weidemann, Proteolytic Processing of the Alzheimer's Disease Amyloid Precursor Protein within Its Cytoplasmic Domain by Caspase-like Proteases. J Biol Chem, 274, 5823-5829, 1999.

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