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研究生: 許雅涵
Hsu, Ya-Han
論文名稱: 光熱誘導癌症免疫治療
Photothermal Induced Cancer Immune Therapy
指導教授: 葉晨聖
Yeh, Chen-Sheng
學位類別: 碩士
Master
系所名稱: 理學院 - 化學系
Department of Chemistry
論文出版年: 2020
畢業學年度: 108
語文別: 中文
論文頁數: 35
中文關鍵詞: 免疫治療光熱治療TLR 9CpG癌症治療
外文關鍵詞: immunotherapy, photothermal therapy, TLR 9, anti-cancer
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  • 在傳統的癌症治療上,腫瘤的轉移跟復發一直都影響治療結果。因此,免疫治療的崛起扮演了一個突破性的角色,在此研究中利用808 nm紅外光誘導金奈米球殼的光熱效應來對腫瘤細胞產生熱傷害,藉由熱相關蛋白干擾細胞內訊息分子的傳遞來促使腫瘤細胞凋亡變成細胞碎片,這些碎片可以當成抗原提供給免疫細胞進行辨識,進而啟動下游的免疫反應;此外,金奈米球殼的光熱性質也促使CpG核苷酸(oligodeoxyribonucleotide, ODN)序列從奈米材料上釋出,誘導免疫細胞上Toll-like receptor(TLR) 9的活化,進而啟動免疫反應的覺醒。這些被喚醒的免疫細胞如同士兵一樣,在細胞激素(cytokines)和趨化因子(chemokines)的引導下遷移至腫瘤部位,藉由辨認腫瘤細胞上的特定抗原來攻擊腫瘤細胞。同時,免疫細胞也會進行全身性的巡視,清除轉移的腫瘤細胞,降低腫瘤治療後轉移以及復發的機率,提升整體的治療成效。

    In traditional cancer therapy, tumor metastasis and recurrence have always affected the anti-cancer therapy, therefore, the rise of immunotherapy has played a critical role. In our study, 808 nm aser was used to induce the photothermal effect of the Au nanoshells to cause thermal damage to induce tumor cells going to apoptosis.
    In addition, the photothermal properties of the Au nanoshells also promote CpG ODN release from the nanomaterials, inducing the activation of Toll-like receptor (TLR) 9, which initiates the awakening of the immune response. These awakened immune cells, like soldiers, migrate to the tumor site under the guidance of cytokines and chemokines, and attack tumor cells by identifying specific antigens on the tumor cells. At the same time, immune cells will also conduct systemic patrols to remove metastatic tumor cells, reduce the probability of metastasis and recurrence after tumor treatment, and improve the overall effectiveness of treatment.

    摘要 i 英文延伸摘要(Extended Abstract) ii INTRODUCTION iii METHODS iii RESULTS AND DISCUSSION iv CONCLUSION x 致謝 xi 目錄 xii 圖目錄 xiv 第一章、 緒論 1 1-1 免疫治療法 1 1-1-1 免疫治療法的歷史發展 1 1-1-2 免疫治療法的種類 2 1-1-3 類鐸受體誘導免疫反應 3 1-1-4 免疫治療法的機制 5 1-2 腫瘤熱療法 6 1-2-1 奈米粒子的光熱效應 7 1-2-2 溫熱促進免疫反應 8 1-2-3 奈米粒子於光熱誘導免疫治療的應用 9 第二章、 實驗藥品與儀器 10 2-1 實驗藥品 10 2-1-1 奈米粒子合成之相關藥品 10 2-2 實驗儀器 12 2-2-1 材料鑑定相關儀器 12 2-2-2 細胞&動物實驗相關儀器 12 第三章、 研究動機與實驗方法 13 3-1 研究動機 13 3-2 實驗方法 14 3-2-1 二氧化矽奈米粒子(SiO2 nanaparticles)的製備 14 3-2-2 修飾胺基於二氧化矽層表面 14 3-2-3 吸附奈米金種於二氧化矽層表面 15 3-2-4 合成奈米金殼包覆二氧化矽奈米粒子 15 3-2-5 修飾寡核苷酸(oligodeoxyribonucleotide, ODN)於金奈米球殼表面 16 3-2-6 利用電泳法(electrophoresis)鑑定寡核苷酸成功修飾於金奈米球殼表面 16 3-2-7 金奈米球殼的升溫速率鑑定 16 3-2-8 利用光熱效應將互補端寡核苷酸從金奈米球殼表面釋放 17 3-2-9 金奈米球殼的細胞毒性測試 17 第四章、 實驗結果與討論 18 4-1金奈米球殼的性質與鑑定 18 4-2 金奈米球殼的光熱效應 19 4-3 使用808奈米的雷射誘導寡核苷酸由金奈米球殼的表面釋放 19 4-4 金奈米球殼對於黑色素瘤細胞的毒性測試 21 4-5 金奈米球殼誘導樹突細胞活化的測試 21 4-6 動物實驗前老鼠腫瘤模型的前測 24 4-7 動物實驗的結果與討論 24 第五章、 結論 31 參考文獻 32

    1. Burnet, F. M.; M.D.; F.R.S., CANCER-A BIOLOGICAL APPROACH. BMJ 1957, 1, 779-787.
    2. Gajewski, T. F.; Schreiber, H.; Fu, Y. X., Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 2013, 14 (10), 1014-22.
    3. Chao, M. P.; Alizadeh, A. A.; Tang, C.; Myklebust, J. H.; Varghese, B.; Gill, S.; Jan, M.; Cha, A. C.; Chan, C. K.; Tan, B. T.; Park, C. Y.; Zhao, F.; Kohrt, H. E.; Malumbres, R.; Briones, J.; Gascoyne, R. D.; Lossos, I. S.; Levy, R.; Weissman, I. L.; Majeti, R., Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell 2010, 142 (5), 699-713.
    4. Du, B.; Jiang, Q.-L.; Cleveland, J.; Liu, B.-R.; Zhang, D., Targeting Toll-like receptors against cancer. Journal of Cancer Metastasis and Treatment 2016, 2 (12).
    5. Gupta, S. K.; Bajwa, P.; Deb, R.; Chellappa, M. M.; Dey, S., Flagellin a toll-like receptor 5 agonist as an adjuvant in chicken vaccines. Clin Vaccine Immunol 2014, 21 (3), 261-70.
    6. Korneev, K. V.; Atretkhany, K. N.; Drutskaya, M. S.; Grivennikov, S. I.; Kuprash, D. V.; Nedospasov, S. A., TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis. Cytokine 2017, 89, 127-135.
    7. Rosin, D. L.; Okusa, M. D., Dangers within: DAMP responses to damage and cell death in kidney disease. J Am Soc Nephrol 2011, 22 (3), 416-25.
    8. Ton N. Schumacher; Schreiber, R. D., Neoantigens in cancer immunotherapy. SCIENCE 2015, 348 (6230), 69-74.
    9. Zhang, Y.; Zhan, X.; Xiong, J.; Peng, S.; Huang, W.; Joshi, R.; Cai, Y.; Liu, Y.; Li, R.; Yuan, K.; Zhou, N.; Min, W., Temperature-dependent cell death patterns induced by functionalized gold nanoparticle photothermal therapy in melanoma cells. Sci Rep 2018, 8 (1), 8720.
    10. Szasz, A.; Iluri, N.; Szasz, O., Local Hyperthermia in Oncology – To Choose or not to Choose? In Hyperthermia, 2013.
    11. Zhang, X.; Du, J.; Guo, Z.; Yu, J.; Gao, Q.; Yin, W.; Zhu, S.; Gu, Z.; Zhao, Y., Efficient Near Infrared Light Triggered Nitric Oxide Release Nanocomposites for Sensitizing Mild Photothermal Therapy. Adv Sci (Weinh) 2019, 6 (3), 1801122.
    12. Gong, L.; Zhang, Q.; Pan, X.; Chen, S.; Yang, L.; Liu, B.; Yang, W.; Yu, L.; Xiao, Z. X.; Feng, X. H.; Wang, H.; Yuan, Z. M.; Peng, J.; Tan, W. Q.; Chen, J., p53 Protects Cells from Death at the Heatstroke Threshold Temperature. Cell Rep 2019, 29 (11), 3693-3707 e5.
    13. Zeng, L.; Tan, J.; Lu, W.; Lu, T.; Hu, Z., The potential role of small heat shock proteins in mitochondria. Cell Signal 2013, 25 (11), 2312-9.
    14. Xing, T.; Gao, F.; Tume, R. K.; Zhou, G.; Xu, X., Stress Effects on Meat Quality: A Mechanistic Perspective. Comprehensive Reviews in Food Science and Food Safety 2019, 18 (2), 380-401.
    15. Boni, R., Heat stress, a serious threat to reproductive function in animals and humans. Mol Reprod Dev 2019, 86 (10), 1307-1323.
    16. Wallace, E. W.; Kear-Scott, J. L.; Pilipenko, E. V.; Schwartz, M. H.; Laskowski, P. R.; Rojek, A. E.; Katanski, C. D.; Riback, J. A.; Dion, M. F.; Franks, A. M.; Airoldi, E. M.; Pan, T.; Budnik, B. A.; Drummond, D. A., Reversible, Specific, Active Aggregates of Endogenous Proteins Assemble upon Heat Stress. Cell 2015, 162 (6), 1286-98.
    17. Jaque, D.; Martinez Maestro, L.; del Rosal, B.; Haro-Gonzalez, P.; Benayas, A.; Plaza, J. L.; Martin Rodriguez, E.; Garcia Sole, J., Nanoparticles for photothermal therapies. Nanoscale 2014, 6 (16), 9494-530.
    18. Willets, K. A.; Van Duyne, R. P., Localized surface plasmon resonance spectroscopy and sensing. Annu Rev Phys Chem 2007, 58, 267-97.
    19. Liang, J.; Liu, H.; Yu, J.; Zhou, L.; Zhu, J., Plasmon-enhanced solar vapor generation. Nanophotonics 2019, 8 (5), 771-786.
    20. Webb, J. A.; Bardhan, R., Emerging advances in nanomedicine with engineered gold nanostructures. Nanoscale 2014, 6 (5), 2502-30.
    21. Evans, S. S.; Repasky, E. A.; Fisher, D. T., Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol 2015, 15 (6), 335-49.
    22. Huang, L.; Li, Y.; Du, Y.; Zhang, Y.; Wang, X.; Ding, Y.; Yang, X.; Meng, F.; Tu, J.; Luo, L.; Sun, C., Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy. Nat Commun 2019, 10 (1), 4871.
    23. Wang, J.; Chang, Y.; Luo, H.; Jiang, W.; Xu, L.; Chen, T.; Zhu, X., Designing immunogenic nanotherapeutics for photothermal-triggered immunotherapy involving reprogramming immunosuppression and activating systemic antitumor responses. Biomaterials 2020, 255, 120153.
    24. Galon, J.; Bruni, D., Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov 2019, 18 (3), 197-218.
    25. Bonaventura, P.; Shekarian, T.; Alcazer, V.; Valladeau-Guilemond, J.; Valsesia-Wittmann, S.; Amigorena, S.; Caux, C.; Depil, S., Cold Tumors: A Therapeutic Challenge for Immunotherapy. Front Immunol 2019, 10, 168.
    26. Wang, M.; Song, J.; Zhou, F.; Hoover, A. R.; Murray, C.; Zhou, B.; Wang, L.; Qu, J.; Chen, W. R., NIR-Triggered Phototherapy and Immunotherapy via an Antigen-Capturing Nanoplatform for Metastatic Cancer Treatment. Adv Sci (Weinh) 2019, 6 (10), 1802157.
    27. Min, Y.; Roche, K. C.; Tian, S.; Eblan, M. J.; McKinnon, K. P.; Caster, J. M.; Chai, S.; Herring, L. E.; Zhang, L.; Zhang, T.; DeSimone, J. M.; Tepper, J. E.; Vincent, B. G.; Serody, J. S.; Wang, A. Z., Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy. Nat Nanotechnol 2017, 12 (9), 877-882.
    28. Klinman, D. M., Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol 2004, 4 (4), 249-58.
    29. Hirsch, L. R.; Gobin, A. M.; Lowery, A. R.; Tam, F.; Drezek, R. A.; Halas, N. J.; West, J. L., Metal nanoshells. Ann Biomed Eng 2006, 34 (1), 15-22.
    30. Anestakis, D.; Petanidis, S.; Kalyvas, S.; Nday, C. M.; Tsave, O.; Kioseoglou, E.; Salifoglou, A., Mechanisms and applications of interleukins in cancer immunotherapy. Int J Mol Sci 2015, 16 (1), 1691-710.
    31. Narayanan Parameswaran; Patial, S., Tumor Necrosis Factor-α Signaling in Macrophages. Crit Rev Eukaryot Gene Expr. 2010, 20, 87-103.

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