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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17054
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor何佳安(Ja-an Annie Ho)
dc.contributor.authorShao-Ching Fengen
dc.contributor.author馮劭擎zh_TW
dc.date.accessioned2021-06-07T23:54:50Z-
dc.date.copyright2020-08-14
dc.date.issued2020
dc.date.submitted2020-08-11
dc.identifier.citation1.Dole, M.; Wilson, F. R.; Fife, W. P., Hyperbaric Hydrogen Therapy - Possible Treatment for Cancer. Science 1975, 190 (4210), 152-154.
2.Ohsawa, I.; Ishikawa, M.; Takahashi, K.; Watanabe, M.; Nishimaki, K.; Yamagata, K.; Katsura, K.; Katayama, Y.; Asoh, S.; Ohta, S., Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007, 13 (6), 688-694.
3.Ge, L.; Yang, M.; Yang, N. N.; Yin, X. X.; Song, W. G., Molecular hydrogen: a preventive and therapeutic medical gas for various diseases. Oncotarget 2017, 8 (60), 102653-102673.
4.Li, S.; Liao, R. R.; Sheng, X. Y.; Luo, X. J.; Zhang, X.; Wen, X. M.; Zhou, J.; Peng, K., Hydrogen Gas in Cancer Treatment. Front Oncol 2019, 9.
5.Yang, Q. X.; Ji, G. D.; Pan, R. T.; Zhao, Y. H.; Yan, P., Protective effect of hydrogen-rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy. Mol Clin Oncol 2017, 7 (5), 891-896.
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7.Kajiyama, S.; Hasegawa, G.; Asano, M.; Hosoda, H.; Fukui, M.; Nakamura, N.; Kitawaki, J.; Imai, S.; Nakano, K.; Ohta, M.; Adachi, T.; Obayashi, H.; Yoshikawa, T., Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 2008, 28 (3), 137-143.
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20.Gao, Y. A.; Yang, H. X.; Fan, Y. B.; Li, L.; Fang, J. H.; Yang, W., Hydrogen-Rich Saline Attenuates Cardiac and Hepatic Injury in Doxorubicin Rat Model by Inhibiting Inflammation and Apoptosis (vol 2016, 1320365, 2016). Mediat Inflamm 2017, 2017.
21.Yang, Y.; Liu, P. Y.; Bao, W.; Chen, S. J.; Wu, F. S.; Zhu, P. Y., Hydrogen inhibits endometrial cancer growth via a ROS/NLRP3/caspase-1/GSDMD-mediated pyroptotic pathway. Bmc Cancer 2020, 20 (1).
22.Fan, M. J.; Wen, Y. Y.; Ye, D.; Jin, Z. K.; Zhao, P. H.; Chen, D. Y.; Lu, X. F.; He, Q. J., Acid-Responsive H-2-Releasing 2D MgB2 Nanosheet for Therapeutic Synergy and Side Effect Attenuation of Gastric Cancer Chemotherapy. Adv Healthc Mater 2019, 8 (13).
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32.Zou, Y. Q.; von Wolff, N.; Anaby, A.; Xie, Y. J.; Milstein, D., Ethylene glycol as an efficient and reversible liquid-organic hydrogen carrier. Nat Catal 2019, 2 (5), 415-422.
33.Hoang, T. K. A.; Morris, L.; Sun, J.; Trudeau, M. L.; Antonelli, D. M., Titanium hydrazide gels for Kubas-type hydrogen storage. J Mater Chem A 2013, 1 (6), 1947-1951.
34.Hamaed, A.; Van Mai, H.; Hoang, T. K. A.; Trudeau, M.; Antonelli, D., Functionalized Porous Silicas with Unsaturated Early Transition Metal Moieties as Hydrogen Storage Materials: Comparison of Metal and Oxidation State. J Phys Chem C 2010, 114 (18), 8651-8660.
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36.Lopez-Corral, I.; Irigoyen, B.; Juan, A., Bonding in PdH2 and Pd2H2 systems adsorbed on carbon nanotubes: Implications for hydrogen storage. Int J Hydrogen Energ 2014, 39 (16), 8780-8790.
37.Hamaed, A.; Hoang, T. K. A.; Trudeau, M.; Antonelli, D. M., Optimization of hydrogen storage capacity in silica-supported low valent Ti systems exploiting Kubas binding of hydrogen. J Organomet Chem 2009, 694 (17), 2793-2800.
38.Yu, X. B.; Tang, Z. W.; Sun, D. L.; Ouyang, L. Z.; Zhu, M., Recent advances and remaining challenges of nanostructured materials for hydrogen storage applications. Prog Mater Sci 2017, 88, 1-48.
39.Zhang, X.; Ren, Z. H.; Zhang, X. L.; Gao, M. X.; Pan, H. G.; Liu, Y. F., Triggering highly stable catalytic activity of metallic titanium for hydrogen storage in NaAlH4 by preparing ultrafine nanoparticles. J Mater Chem A 2019, 7 (9), 4651-4659.
40.Li, L. L.; Yang, M.; Dong, Y.; Mei, P.; Cheng, H. S., Hydrogen storage and release from a new promising Liquid Organic Hydrogen Storage Carrier (LOHC): 2-methylindole. Int J Hydrogen Energ 2016, 41 (36), 16129-16134.
41.Carraro, P. M.; Sapag, K.; Oliva, M. I.; Eimer, G. A., Comparative study of hydrogen storage on metal doped mesoporous materials. Chem Phys Lett 2018, 701, 93-97.
42.Kamegawa, T.; Nakaue, T., Complete hydrogen release from aqueous ammonia-borane over a platinum-loaded titanium dioxide photocatalyst. Chem Commun 2015, 51 (94), 16802-16805.
43.Hamaed, A.; Trudeau, M.; Antonelli, D. M., H-2 storage materials (22KJ/mol) using organometallic Ti fragments as sigma-H-2 binding sites. J Am Chem Soc 2008, 130 (22), 6992-6999.
44.Navlani-Garcia, M.; Mori, K.; Kuwahara, Y.; Yamashita, H., Recent strategies targeting efficient hydrogen production from chemical hydrogen storage materials over carbon-supported catalysts. Npg Asia Mater 2018, 10, 277-292.
45.Zhang, L. J.; Xia, G. L.; Ge, Y.; Wang, C. Y.; Guo, Z. P.; Li, X. G.; Yu, X. B., Ammonia borane confined by nitrogen-containing carbon nanotubes: enhanced dehydrogenation properties originating from synergetic catalysis and nanoconfinement. J Mater Chem A 2015, 3 (41), 20494-20499.
46.Yan, J. M.; Zhang, X. B.; Han, S.; Shioyama, H.; Xu, Q., Magnetically recyclable Fe-Ni alloy catalyzed dehydrogenation of ammonia borane in aqueous solution under ambient atmosphere. J Power Sources 2009, 194 (1), 478-481.
47.Bluhm, M. E.; Bradley, M. G.; Butterick, R.; Kusari, U.; Sneddon, L. G., Amineborane-based chemical hydrogen storage: Enhanced ammonia borane dehydrogenation in ionic liquids. J Am Chem Soc 2006, 128 (24), 7748-7749.
48.Denney, M. C.; Pons, V.; Hebden, T. J.; Heinekey, D. M.; Goldberg, K. I., Efficient catalysis of ammonia borane dehydrogenation. J Am Chem Soc 2006, 128 (37), 12048-12049.
49.Keaton, R. J.; Blacquiere, J. M.; Baker, R. T., Base metal catalyzed dehydrogenation of ammonia-borane for chemical hydrogen storage. J Am Chem Soc 2007, 129 (7), 1844-+.
50.Xiong, Z. T.; Yong, C. K.; Wu, G. T.; Chen, P.; Shaw, W.; Karkamkar, A.; Autrey, T.; Jones, M. O.; Johnson, S. R.; Edwards, P. P.; David, W. I. F., High-capacity hydrogen storage in lithium and sodium amidoboranes. Nat Mater 2008, 7 (2), 138-141.
51.Peng, B.; Chen, J., Ammonia borane as an efficient and lightweight hydrogen storage medium. Energ Environ Sci 2008, 1 (4), 479-483.
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53.Ge, Y. Z.; Shah, Z. H.; Lin, X. J.; Lu, R. W.; Liao, Z. M.; Zhang, S. F., Highly Efficient Pt Decorated CoCu Bimetallic Nanoparticles Protected in Silica for Hydrogen Production from Ammonia-Borane. Acs Sustain Chem Eng 2017, 5 (2), 1675-1684.
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55.Yao, Q. L.; Lu, Z. H.; Zhang, Z. J.; Chen, X. S.; Lan, Y. Q., One-pot synthesis of core-shell Cu@SiO2 nanospheres and their catalysis for hydrolytic dehydrogenation of ammonia borane and hydrazine borane. Sci Rep-Uk 2014, 4.
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58.Rakap, M.; Ozkar, S., Hydrogen generation from the hydrolysis of ammonia-borane using intrazeolite cobalt(0) nanoclusters catalyst. Int J Hydrogen Energ 2010, 35 (8), 3341-3346.
59.Liu, P. L.; Gu, X. J.; Kang, K.; Zhang, H.; Cheng, J.; Su, H. Q., Highly Efficient Catalytic Hydrogen Evolution from Ammonia Borane Using the Synergistic Effect of Crystallinity and Size of Noble-Metal-Free Nanoparticles Supported by Porous Metal Organic Frameworks. Acs Appl Mater Inter 2017, 9 (12), 10759-10767.
60.Torney, F.; Trewyn, B. G.; Lin, V. S. Y.; Wang, K., Mesoporous silica nanoparticles deliver DNA and chemicals into plants. Nat Nanotechnol 2007, 2 (5), 295-300.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17054-
dc.description.abstract早在 1975 年氫氣被發現具有治療小鼠皮膚麟狀癌的功能後,便揭開了科學家們對氫氣在生物醫學的一系列研究。氫氣的主要功能包括:(1) 中和生物體內活性氧化物(ROS)達到抗氧化的效果,(2) 調控發炎因子以抑制發炎反應,(3) 藉由調節生長因子或細胞凋亡因子以抑制腫瘤的生長。氫氣的給藥方式可分為口服(喝氫水),吸入(吸氫氣)及注射(氫氣食鹽水)三種,但由於氫氣的分子極小、容易溢散且滯留性差,因此限制了氫氣治療的效果。此外,如何運送氫氣標靶至腫瘤細胞也是亟欲改善的重點。因此,在本研究的目標為開發可以有效治療癌症的新型產氫奈米載體。此奈米載體主要由三項元件組合而成:(1) 以硼烷氨(ammonia borane, AB)為儲氫材料;(2) 中孔奈米矽球(MSN)為藥物載體;(3) 以金奈米粒子催化 AB 產氫的效率。我們的初步實驗成果證實此一載體可以在腫瘤微環境中酸性環境下(pH 6.5〜6.9)增強金奈米粒子催化 AB 的效率,並藉由 MSN 賦予其標靶性,而後因為氫氣可從載體被緩效釋放,增加滯留性,三效合一使該產氫奈米載體可以累積在病灶提供持續性氫氣治療,達到顯著抑制癌細胞生長的效果。zh_TW
dc.description.abstractHydrogen was first reported in 1975 to have therapeutic effects in a skin squamous carcinoma mouse model. The main function of hydrogen as a therapeutic agent was to selectively quench detrimental reactive oxygen species (ROS) resulted in antioxidation. Furthermore, molecular hydrogen was able to regulate inflammatory factors to inhibit the inflammation, and to regulate growth/apoptotic factors to impede tumor growth. The common methods of hydrogen administration include oral route (drinking H2-dissolved water), inhalation (inhaling hydrogen gas), and intravenous injection (injecting H2-dissolved saline); however, the high diffusibility and low solubility of hydrogen often limited the efficacy of hydrogen therapy. Therefore, we believe that a nanomedicine strategy tailors to need by specific disease conditions would be a perfect solution for it. Our nanocarrier is composed of three components: the first is ammonia borane (AB), serving as a hydrogen producer, and the second is mesoporous silica nanoparticle, functioning as a carrier, the third is the gold nanoparticles, participating in speeding up the hydrogen production. Also this carrier is acid-responsive, the tumor microenviroment (TME)-triggered drug release enabled the efficient generation of H2. Preliminary results confirmed that our nanomedicine strategy enhance outcome of hydrogen therapy.en
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dc.description.tableofcontents目錄
第一章 緒論 1
1.1 當前癌症治療方法 1
1.2 氫氣治療發展 3
1.3 氫氣治療可降低生物體內活性氧化物 ( ROS ) 及調控抗氧化相關酵素 5
1.4 氫氣治療可調控之訊號分子 7
1.5 儲氫及產氫奈米載體的發展 8
1.6 產氫化合物-硼烷氨 10
1.7 介孔二氧化矽奈米粒子 10
第二章 研究動機,方向與實驗設計 12
2.1 研究動機 12
2.2 實驗設計之方向與設計 13
第三章 實驗材料與方法 17
3.1 細胞株及細胞培養 17
3.1.1 胚胎成纖維細胞-NIH/3T3 ( BCRC Number:60008 ) 17
3.1.2 路易士肺腺癌細胞-LL/2 (BCRC Number:60050) 17
3.1.3 細胞培養 18
3.1.4 凍細胞與細胞解凍 18
3.2 台盼藍染色 (Trypan blue staining) 18
3.3 細胞存活率測試(MTT cell viability assay) 19
3.4 細胞mRNA萃取與反轉錄 (Cell’s mRNA extraction and Reverse Transcription) 20
3.4.1 mRNA萃取 20
3.4.2 mRNA定量 21
3.4.3 反轉錄 21
3.5 聚合酶鏈鎖反應 (Polymerase Chain Reaction, PCR) 21
3.6 西方點墨法 ( Western blotting assay ) 24
3.6.1 蛋白質萃取 24
3.6.2 蛋白質定量 24
3.6.3 蛋白質電泳凝膠 ( SDS-PAGE ) 製備 25
3.6.4 SDS-PAGE蛋白質膠體電泳條件 25
3.6.5 蛋白質樣本轉印 26
3.6.6 免疫墨點法 ( Immuno-blotting ) 26
3.7 Caspase-3 Assay Kit ( Colorimetric ) ( 購自伯森生物科技 ) 27
3.8 流式細胞儀分析 ( Flow cytometric analysis ) 27
3.9 氫氣濃度測定 28
3.10 細胞內氧化自由基測定 ( Intracellular reactive oxygen species;ROS ) 30
3.11 產氫奈米載體合成 ( AB-Au@MSN ) 31
3.11.1 介孔二氧化矽奈米粒子合成 ( mesoporous silica nanoparticles, MSN ) 31
3.11.2 APTMS-MCM48制備 32
3.11.3 Au-APTMS-MCM48製備 34
3.11.4 硼烷氨含浸 35
3.12 產氫奈米載體之產氫效率測試 36
3.13 即時無標記細胞分析 (RTCA) 38
3.14 實驗材料 39
3.14.1 藥品 39
3.14.2 試劑 41
3.14.3 抗體 41
3.14.4 實驗儀器 42
第四章 實驗結果與討論 44
4.1 建立氫氣治療細胞平台 44
4.2 氫氣及產氫奈米載體對細胞存活率的影響 45
4.3 以RTCA分析產氫奈米載體於pH 7.4及pH 6對癌細胞之抑制效果 50
4.4 氫氣對細胞生長因子的調控 52
4.5 以流式細胞儀分析探討氫氣對細胞死亡路徑之影響 ( Annexin V / PI ) 54
4.6 氫氣對細胞凋亡的調控 57
4.7 氫氣對細胞焦亡的調控 60
第五章 結果討論及未來展望 64
第六章 參考文獻 65
dc.language.isozh-TW
dc.title開發新型產氫奈米載體應用於癌症治療之研究zh_TW
dc.titleDevelopment of novel hydrogen gas generating nanoparticle for cancer therapyen
dc.typeThesis
dc.date.schoolyear108-2
dc.description.degree碩士
dc.contributor.oralexamcommittee吳立真(Li-chen Wu),徐士蘭(Shih-Lan Hsu),呂瑞梅(Jui-Mei Lu),楊家銘(Chia-Min Yan)
dc.subject.keyword氫氣治療,產氫奈米載體,抗氧化,抑制發炎反應,調節生長因子或細胞凋亡因子,抑制癌細胞生長,zh_TW
dc.subject.keywordHydrogen therapy,nanomedicine,antioxidation,inhibit the inflammation,regulate growth/apoptotic factors,impede tumor growth,en
dc.relation.page74
dc.identifier.doi10.6342/NTU202002634
dc.rights.note未授權
dc.date.accepted2020-08-11
dc.contributor.author-college生命科學院zh_TW
dc.contributor.author-dept生化科技學系zh_TW
顯示於系所單位:生化科技學系

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