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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅禮強 | zh_TW |
| dc.contributor.advisor | Lee-Chiang Lo | en |
| dc.contributor.author | 鍾博任 | zh_TW |
| dc.contributor.author | Po-Jen Chung | en |
| dc.date.accessioned | 2021-07-11T15:06:01Z | - |
| dc.date.available | 2024-08-19 | - |
| dc.date.copyright | 2019-08-23 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1. Lee, S. H.; Gupta, M. K.; Bang, J. B.; Bae, H.; Sung, H.-J., Current progress in reactive oxygen species (ROS)-responsive materials for biomedical applications. Adv. Healthc. Mater. 2013, 2, 908-915.
2. Trachootham, D.; Alexandre, J.; Huang, P., Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat. Rev. Drug Discov. 2009, 8, 579-591. 3. Brieger, K.; Schiavone, S.; Miller Jr, F. J.; Krause, K.-H., Reactive oxygen species: from health to disease. Swiss Med. Wkly. 2012, 142, w13659. 4. Schumacker, P. T., Reactive oxygen species in cancer: a dance with the devil. Cancer cell 2015, 27, 156-157. 5. Song, C. C.; Du, F.-S.; Li, Z. C., Oxidation-responsive polymers for biomedical applications. J. Mater. Chem. B 2014, 2, 3413-3426. 6. Loukogeorgakis, S. P.; van den Berg, M. J.; Sofat, R.; Nitsch, D.; Charakida, M.; Haiyee, B. H.; de Groot, E.; MacAllister, R. J.; Kuijpers, T. W.; Deanfield, J. E., Role of NADPH oxidase in endothelial ischemia/reperfusion injury in humans. Circulation 2010, 121, 2310. 7. Sorce, S.; Krause, K.-H., NOX enzymes in the central nervous system: from signaling to disease. Antioxidants Redox S. 2009, 11, 2481-2504. 8. Saravanakumar, G.; Kim, J.; Kim, W. J., Reactive-oxygen-species-responsive drug delivery systems: promises and challenges. Adv. Sci. 2016, 4, 1600124-1600124. 9. Schieber, M.; Chandel, N. S., ROS function in redox signaling and oxidative stress. Curr. Biol. 2014, 24, 453-462. 10. Lallana, E.; Tirelli, N., Oxidation-responsive polymers: Which groups to use, how to make them, hhat to expect from them (biomedical applications). Macromol. Chem. Physic. 2013, 214 , 143-158. 11. Ma, N.; Li, Y.; Xu, H.; Wang, Z.; Zhang, X., Dual redox responsive assemblies formed from diselenide block copolymers. J. Am. Chem. Soc. 2010, 132, 442-443. 12. Deepagan, V. G.; Kwon, S.; You, D. G.; Nguyen, V. Q.; Um, W.; Ko, H.; Lee, H.; Jo, D.-G.; Kang, Y. M.; Park, J. H., In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery. Biomaterials 2016, 103, 56-66. 13. Liu, L. H.; Qiu, W. X.; Li, B.; Zhang, C.; Sun, L. F.; Wan, S. S.; Rong, L.; Zhang, X. Z., A red light activatable multifunctional prodrug for image-guided photodynamic therapy and cascaded chemotherapy. Adv. Funct. Mater. 2016, 26 , 6257-6269. 14. Han, K.; Zhu, J. Y.; Wang, S. B.; Li, Z. H.; Cheng, S. X.; Zhang, X. Z., Tumor targeted gold nanoparticles for FRET-based tumor imaging and light responsive on-demand drug release. J. Mater. Chem. B 2015, 3, 8065-8069. 15. Broaders, K. E.; Grandhe, S.; Fréchet, J. M. J., A Biocompatible oxidation-triggered carrier polymer with potential in therapeutics. J. Am. Chem. Soc. 2011, 133, 756-758. 16. de Gracia Lux, C.; Joshi-Barr, S.; Nguyen, T.; Mahmoud, E.; Schopf, E.; Fomina, N.; Almutairi, A., Biocompatible polymeric nanoparticles degrade and release cargo in response to biologically relevant levels ofhydrogen peroxide. J. Am. Chem. Soc. 2012, 134, 15758-15764. 17. Yuan, Y.; Zhang, C. J.; Liu, B., A Photoactivatable AIE polymer for light-controlled gene delivery: concurrent endo/lysosomal escape and DNA unpacking. Angew. Chem. Int. Edit. 2015, 54 , 11419-11423. 18. Hossion, A. M. L.; Bio, M.; Nkepang, G.; Awuah, S. G.; You, Y., Visible light controlled release of anticancer drug through double activation of prodrug. ACS. Med. Chem. Lett. 2013, 4, 124-127. 19. Yu, S. S.; Koblin, R. L.; Zachman, A. L.; Perrien, D. S.; Hofmeister, L. H.; Giorgio, T. D.; Sung, H.-J., Physiologically relevant oxidative degradation of oligo(proline) cross-linked polymeric scaffolds. Biomacromolecules 2011, 12 , 4357-4366. 20. Gupta, M. K.; Lee, S. H.; Crowder, S. W.; Wang, X.; Hofmeister, L. H.; Nelson, C. E.; Bellan, L. M.; Duvall, C. L.; Sung, H.-J., Oligoproline-derived nanocarrier for dual stimuli-responsive gene delivery. J. Mater. Chem. B 2015, 3, 7271-7280. 21. Kwon, J.; Kim, J.; Park, S.; Khang, G.; Kang, P. M.; Lee, D., Inflammation-responsive antioxidant nanoparticles based on a polymeric prodrug of vanillin. Biomacromolecules 2013, 14, 1618-1626. 22. Li, J.; Ke, W.; Wang, L.; Huang, M.; Yin, W.; Zhang, P.; Chen, Q.; Ge, Z., Self-sufficing H2O2-responsive nanocarriers through tumor-specific H2O2 production for synergistic oxidation-chemotherapy. J. Control. Release 2016, 225, 64-74. 23. Wu, E. C.; Park, J.-H.; Park, J.; Segal, E.; Cunin, F.; Sailor, M. J., Oxidation-triggered release of fluorescent molecules or drugs from mesoporous si microparticles. ACS. Nano. 2008, 2, 2401-2409. 24. Kataoka, K.; Harada, A.; Nagasaki, Y., Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv. Drug Deliver. Rev. 2001, 47, 113-131. 25. Oerlemans, C.; Bult, W.; Bos, M.; Storm, G.; Nijsen, J. F. W.; Hennink, W. E., Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm. Res. 2010, 27, 2569-2589. 26. Gong, J.; Chen, M.; Zheng, Y.; Wang, S.; Wang, Y., Polymeric micelles drug delivery system in oncology. J.Control. Release 2012, 159, 312-323. 27. Torchilin, V. P., Micellar nanocarriers: pharmaceutical perspectives. Pharm. Res. 2006, 24, 1-16. 28. Dinarvand, R.; Sepehri, N.; Manoochehri, S.; Rouhani, H.; Atyabi, F., Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents. Int. J. Nanomed. 2011, 6, 877-895. 29. Kuang, Y.; Balakrishnan, K.; Gandhi, V.; Peng, X., Hydrogen peroxide inducible DNA cross-linking agents: targeted anticancer prodrugs. J. Am. Chem. Soc. 2011, 133, 19278-19281. 30. Doskey, C. M.; Buranasudja, V.; Wagner, B. A.; Wilkes, J. G.; Du, J.; Cullen, J. J.; Buettner, G. R., Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy. Redox. Biol. 2016, 10, 274-284. 31. Schoenfeld, J. D.; Sibenaller, Z. A.; Mapuskar, K. A.; Wagner, B. A.; Cramer-Morales, K. L.; Furqan, M.; Sandhu, S.; Carlisle, T. L.; Smith, M. C.; Abu Hejleh, T.; Berg, D. J.; Zhang, J.; Keech, J.; Parekh, K. R.; Bhatia, S.; Monga, V.; Bodeker, K. L.; Ahmann, L.; Vollstedt, S.; Brown, H.; Kauffman, E. P. S.; Schall, M. E.; Hohl, R. J.; Clamon, G. H.; Greenlee, J. D.; Howard, M. A.; Schultz, M. K.; Smith, B. J.; Riley, D. P.; Domann, F. E.; Cullen, J. J.; Buettner, G. R.; Buatti, J. M.; Spitz, D. R.; Allen, B. G., O2- and H2O2-mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer cell 2017, 32, 268-268. 32. Kim, E. J.; Bhuniya, S.; Lee, H.; Kim, H. M.; Cheong, C.; Maiti, S.; Hong, K. S.; Kim, J. S., An activatable prodrug for the treatment of metastatic tumors. J. Am. Chem. Soc. 2014, 136, 13888-13894. 33. Yuan, Y.; Liu, J.; Liu, B., Conjugated-polyelectrolyte-based polyprodrug: targeted and image-guided photodynamic and chemotherapy with on-demand drug release upon irradiation with a single light source. Angew. Chem. Int. Edit. 2014, 53, 7163-7168. 34. Fruehauf, J. P.; Meyskens, F. L., Reactive oxygen species: a breath of life or death? Clin. Cancer Res. 2007, 13, 789-794. 35. Hulsman, N.; Medema, J. P.; Bos, C.; Jongejan, A.; Leurs, R.; Smit, M. J.; de Esch, I. J. P.; Richel, D.; Wijtmans, M., Chemical insights in the concept of hybrid drugs: the antitumor effect of nitric oxide-donating aspirin involves a quinone methide but not nitric oxide nor aspirin. J. Med. Chem. 2007, 50, 2424-2431. 36. Kimani, S. G.; Shmigol, T. A.; Hammond, S.; Phillips, J. B.; Bruce, J. I.; MacRobert, A. J.; Malakhov, M. V.; Golding, J. P., Fully Protected glycosylated zinc (II) phthalocyanine shows high uptake and photodynamic cytotoxicity in MCF-7 cancer cells. Photochem. Photobiol. 2013, 89, 139-149. 37. Diehn, M.; Cho, R. W.; Lobo, N. A.; Kalisky, T.; Dorie, M. J.; Kulp, A. N.; Qian, D.; Lam, J. S.; Ailles, L. E.; Wong, M.; Joshua, B.; Kaplan, M. J.; Wapnir, I.; Dirbas, F. M.; Somlo, G.; Garberoglio, C.; Paz, B.; Shen, J.; Lau, S. K.; Quake, S. R.; Brown, J. M.; Weissman, I. L.; Clarke, M. F., Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009, 458, 780-783. 38. Hanot, M.; Boivin, A.; Malésys, C.; Beuve, M.; Colliaux, A.; Foray, N.; Douki, T.; Ardail, D.; Rodriguez-Lafrasse, C., Glutathione depletion and carbon ion radiation potentiate clustered DNA lesions, cell death and prevent chromosomal changes in cancer cells progeny. PLoS One 2012, 7, e44367-e44367. 39. Schumacker, P. T., Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell 2006, 10, 175-176. 40. Raj, L.; Ide, T.; Gurkar, A. U.; Foley, M.; Schenone, M.; Li, X.; Tolliday, N. J.; Golub, T. R.; Carr, S. A.; Shamji, A. F.; Stern, A. M.; Mandinova, A.; Schreiber, S. L.; Lee, S. W., Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 2011, 475, 231-234. 41. Alexandre, J.; Batteux, F.; Nicco, C.; Chéreau, C.; Laurent, A.; Guillevin, L.; Weill, B.; Goldwasser, F., Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo. Int. J. Cancer 2006, 119, 41-48. 42. Noh, J.; Kwon, B.; Han, E.; Park, M.; Yang, W.; Cho, W.; Yoo, W.; Khang, G.; Lee, D., Amplification of oxidative stress by a dual stimuli-responsive hybrid drug enhances cancer cell death. Nat. Commun. 2015, 6, 6907. 43. Wheate, N. J.; Walker, S.; Craig, G. E.; Oun, R., The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton t. 2010, 39, 8113-8127. 44. Schiller, J. H.; Harrington, D.; Belani, C. P.; Langer, C.; Sandler, A.; Krook, J.; Zhu, J.; Johnson, D. H., Comparison of four chemotherapy regimens for advanced non–small-cell lung cancer. New England J. Med. 2002, 346, 92-98. 45. Danhier, F.; Feron, O.; Préat, V., To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J. Control. Release 2010, 148, 135-146. 46. Stuart, M. A. C.; Huck, W. T. S.; Genzer, J.; Müller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, I.; Tsukruk, V. V.; Urban, M.; Winnik, F.; Zauscher, S.; Luzinov, I.; Minko, S., Emerging applications of stimuli-responsive polymer materials. Nat. Mater. 2010, 9, 101. 47. Wang, Y.; Wei, G.; Zhang, X.; Xu, F.; Xiong, X.; Zhou, S., A Step-by-step multiple stimuli-responsive nanoplatform for enhancing combined chemo-photodynamic therapy. Adv. Mater. 2017, 29, 1605357. 48. Wu, S. H.; Hung, Y.; Mou, C. Y., Mesoporous silica nanoparticles as nanocarriers. Chem. Commun. 2011, 47 , 9972-9985. 49. Kung, H. N.; Lu, K. S.; Chau, Y. P., The chemotherapeutic effects of lapacho tree extract: β-lapachone. Chemotherapy 2014, 3, 131-135. 50. Wu, Y.; Wang, X.; Chang, S.; Lu, W.; Liu, M.; Pang, X., β-Lapachone induces NAD(P)H:quinone oxidoreductase-1– and oxidative stress–dependent heat shock protein 90 cleavage and inhibits tumor growth and angiogenesis. J. Pharmacol. Exp. Ther. 2016, 357, 466. 51. Silvers, M. A.; Deja, S.; Singh, N.; Egnatchik, R. A.; Sudderth, J.; Luo, X.; Beg, M. S.; Burgess, S. C.; DeBerardinis, R. J.; Boothman, D. A., The NQO1 bioactivatable drug, β-lapachone, alters the redox state of NQO1+ pancreatic cancer cells, causing perturbation in central carbon metabolism. J. Biol. Chem. 2017, 292, 18203-18216. 52. Ma, X.; Huang, X.; Moore, Z.; Huang, G.; Kilgore, J. A.; Wang, Y.; Hammer, S.; Williams, N. S.; Boothman, D. A.; Gao, J., Esterase-activatable β-lapachone prodrug micelles for NQO1-targeted lung cancer therapy. J. Control. Release 2015, 200, 201-211. 53. Ishiyama, T.; Murata, M.; Miyaura, N., Palladium(0)-catalyzed cross-coupling reaction of alkoxydiboron with haloarenes: a direct procedure for arylboronic esters. J. Org. Chem. 1995, 60, 7508-7510. 54. Yuen, A. K. L.; Hutton, C. A., Deprotection of pinacolyl boronate esters via hydrolysis of intermediate potassium trifluoroborates. Tetrahedron Lett. 2005, 46, 7899-7903. 55. Churches, Q. I.; Hooper, J. F.; Hutton, C. A., A general method for interconversion of boronic acid protecting groups: trifluoroborates as common intermediates. J.f Org. Chem. 2015, 80, 5428-5435. 56. Liang, J.; Zhang, Z.; Zhao, H.; Wan, S.; Zhai, X.; Zhou, J.; Liang, R.; Deng, Q.; Wu, Y.; Lin, G., Simple and rapid monitoring of doxorubicin using streptavidin-modified microparticle-based time-resolved fluorescence immunoassay. RSC. Adv. 2018, 8, 15621-15631. 57. Lo, L.C.; Chu, C.Y., Development of highly selective and sensitive probes for hydrogen peroxide. Chem commun 2003, 21, 2728-2729. 58. Friscourt, F.; Fahrni, C. J.; Boons, G. J., A fluorogenic probe for the catalyst-free detection of azide-tagged molecules. J Am Chem Soc 2012, 134, 18809-18815. 59. Katoh, T.; Monma, H.; Wakasugi, J.; Narita, K.; Katoh, T., Synthesis of β-lapachone, a potential anticancer agent from the lapacho tree. european J Org Chem 2014, 2014, 7099-7103. 60. Lim, S. M.; Jeong, Y.; Lee, S.; Im, H.; Tae, H. S.; Kim, B. G.; Park, H. D.; Park, J.; Hong, S., Identification of β-lapachone analogs as novel MALT1 inhibitors to treat an aggressive subtype of diffuse large B-Cell lymphoma. J Med Chem 2015, 58, 8491-8502. 61. Li, F.; Dong, J.; Hu, X.; Gong, W.; Li, J.; Shen, J.; Tian, H.; Wang, J., A covalent approach for site-specific RNA labeling in mammalian cells. Angew. Chem. Int. Edit. 2015, 54, 4597-4602. 62. Trindade, A. F.; Frade, R. F.; Maçôas, E. M.; Graça, C.; Rodrigues, C. A.; Martinho, J. M.; Afonso, C. A., “Click and go”: simple and fast folic acid conjugation. Org. biomol. chem. 2014, 12, 3181-3190. 63. O’Brien, J. G. K.; Chintala, S. R.; Fox, J. M., Stereoselective synthesis of bicyclo[6.1.0]nonene precursors of the bioorthogonal reagents s-TCO and BCN. J. Org. Chem. 2018, 83, 7500-7503. 64. Dommerholt, J.; Schmidt, S.; Temming, R.; Hendriks, L. J. A.; Rutjes, F. P. J. T.; van Hest, J. C. M.; Lefeber, D. J.; Friedl, P.; van Delft, F. L., Readily accessible bicyclononynes for bioorthogonal labeling and three-dimensional imaging of living cells. Ange. Chem. Int. Edit. 2010, 49 , 9422-9425. 65. Taylor, M. T.; Blackman, M. L.; Dmitrenko, O.; Fox, J. M., Design and synthesis of highly reactive dienophiles for the tetrazine–trans-cyclooctene ligation. J. Am. Chem. Soc. 2011, 133, 9646-9649. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78592 | - |
| dc.description.abstract | 由於在特定病理狀況下常伴隨細胞內積累異常高濃度的過氧化氫(H2O2)的現象，因此本研究室在2003年首創以苯硼酸酯(arylboronate ester)為基本架構，發展出能選擇性與過氧化氫作用的探針分子。本論文延續此一架構，來設計並合成出一系列可藉由過氧化氫來啟動的分子工具；其中包括（一）以抗癌藥物阿黴素(Doxorubicin)為酬載的前驅藥物，利用前驅藥物與介孔二氧化矽納米粒子(Mesoporous silica nanoparticle)結合來探討此選擇性運輸系統(Drug Delivery Systems, DDS)，以及前驅藥物的活化與釋放效能。此外，亦在硼酸酯的苯環上修飾硝基，嘗試利用其拉電子基的特性來提高其對過氧化氫的反應性，以改善原本硼酸酯低反應性的問題。（二）嘗試合成帶有苯硼酸酯啟動端的多官能基重要中間體，此中間體具有可搭配雙酬載的特性，其中Benzylic alcohol的部份可用以連接可經由過氧化氫作用而被釋放的酬載，而結構末端含有以聚乙二醇(Polyethylene glycol)來橋接的疊氮基(azide)則可應用點擊化學(Click chemistry)來引入另一酬載。為了測點及化學的效能，我們合成出具有標靶功能的基團如葉酸等的bicyclo[6.1.0]nonyne (BCN)衍生物。（三）β-拉帕醌及其衍生物的合成。β-拉帕醌為天然產物，可與細胞中NADPH氧化還原酶反應產生活性含氧物，提高細胞中過氧化氫的濃度。由於NADPH氧化還原酶在特定癌細胞中有過量表達的現象，因此我們希望探討β-拉帕醌及其衍生物能否促進硼酸酯與過氧化氫的反應，以提高癌細胞中藥物釋放的效率。綜合上述實驗結果，我們成功獲得了一部分分子工具並且測試其與過氧化氫反應的選擇性，但另一部分在藥物酬載上的純化並不容易，因此我們考慮在將來以結構較簡單的螢光團例如香豆素作為酬載的分子，希望能夠解決純化上的困難。 | zh_TW |
| dc.description.abstract | There are increasing evidences to point out that many pathological conditions are related to abnormal high level of reactive oxygen species (ROS) such as H2O2. Therefore, our laboratory first developed the molecular probes of aryl boronate ester that interacts selectively with hydrogen peroxide in 2003. This thesis continues this framework to design and synthesize a series of molecular tools that can be activated by hydrogen peroxide which include : (1) a prodrug based on the anticancer drug (Doxorubicin), which uses a combination of a prodrug and mesoporous silica nanoparticles to explore this selective drug delivery system (DDS), activation, and release efficacy of prodrugs. In addition, the nitro group is also modified on the benzene ring of the boric acid ester, and attempts are made to improve the reactivity to hydrogen peroxide by utilizing the characteristics of the electron-withdrawing group to improve the problem of low reactivity of the original boronic acid ester. (2) Attempting to synthesize a polyfunctional intermediate with a phenylborate, which has the property of being compatible with double-paying, wherein a part of benzylic alcohol can be used to connect and be released via hydrogen peroxide. The azide, which is bridged with polyethylene glycol at the end of the structure, can be click chemistry to introduce another payload. To test the potency of click chemistry, we also synthesized bicyclo[6.1.0]nonyne (BCN) derivatives with a
target functional group such as folic acid. (3) Synthesis of β-lapachone and its derivatives. β-lapachone is a catechol that reacts with NADPH oxidoreductase in cells to produce ROS, increasing the concentration of hydrogen peroxide in the cells. Because of the overexpression of NADPH oxidoreductase in specific cancer cells, we hope to investigate whether β-lapachone and its derivatives can promote the reaction of borate with hydrogen peroxide to increase drug release in cancer cells effectively. We ave successfully obtained some molecular tools and tested their selectivity for reaction with hydrogen peroxide, but the purification of the other part on the drug ayload is not easy, so we consider to use a simpler fluorophore like coumarin in the future as a molecule for the payload. Therefore, the synthesis step should be carried out and purified more esaily. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:06:01Z (GMT). No. of bitstreams: 1 ntu-108-R06223172-1.pdf: 6820596 bytes, checksum: a5c94f78b2d3d107d93bbf2fbb1f6dcc (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II 目錄 IV 圖目錄 VII 反應式目錄 IX 表目錄 X 縮寫目錄 XI 第一章 緒論 1 1.1 活性含氧物響應系統中的分類 2 1.1.1 透過聚合奈米粒子釋放活性含氧物響應的藥物 2 1.1.2 可經由活性含氧物響應的前驅藥 3 1.2 活性含氧物響應系統的催化機制 5 1.3 特定疾病與其活性含氧物濃度 6 1.4 針對活性含氧物類響應藥物的應用 7 1.4.1 活性含氧物響應前驅藥以及螢光團 8 1.4.2 聚合活性含氧物響應前驅藥 8 1.4.3 活性含氧物雙響應的藥物 10 1.5 實驗目的 11 1.5.1 介孔二氧化矽納米粒子(Mesoporous silica nanoparticle) 11 1.5.2 抗癌藥物阿黴素(DOX)的前驅藥以及藥物遞送系統 12 1.5.3 抗癌藥物阿黴素(DOX)前驅藥的修飾與功能化 13 1.5.4利用拉帕醌提高癌細胞中活性含氧物濃度導致前驅藥釋放 14 第二章 結果與討論 15 2.1. MSN-BDOX之逆合成分析 15 2.2 合成分析及討論 16 2.2.1 化合物3之合成 16 2.2.2 化合物4之合成 22 2.3 活性含氧物響應實驗結果 23 2.3.1 前驅藥4與過氧化氫的反應性 23 2.4 發展以前驅藥4為基礎的藥物遞送系統 25 2.4.1 化合物11之合成 26 2.4.2 藥物遞送系統12之合成 28 2.4.3 前驅藥4設計之結論 30 2.5 前驅藥19之設計 30 2.5.1 前驅藥19之合成 31 2.5.2 前驅藥19設計之結論 33 2.6 功能化前驅藥之設計 33 2.6.1 連接橋—化合物22之合成 33 2.6.2 中間體—化合物26之合成 34 2.6.3 功能化前驅藥28之合成 36 2.7 β-拉帕醌及衍生物之合成 39 2.7.1 β-拉帕醌之合成 39 2.7.2 β-拉帕醌衍生物之合成 39 2.8 具有BCN結構葉酸之合成 40 2.9 結論 41 第三章 實驗部分 42 3.1 一般敘述 42 3.2 有機合成實驗步驟及光譜數據 44 參考文獻 74 附錄 86 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 前驅藥 | zh_TW |
| dc.subject | 活性含氧物響應載體系統 | zh_TW |
| dc.subject | 苯硼酸酯 | zh_TW |
| dc.subject | 介孔二氧化矽納米粒子 | zh_TW |
| dc.subject | 阿黴素 | zh_TW |
| dc.subject | β-拉帕? | zh_TW |
| dc.subject | 點擊化學 | zh_TW |
| dc.subject | β-lapachone | en |
| dc.subject | Prodrug | en |
| dc.subject | ROS-responsive carrier system | en |
| dc.subject | doxorubicin | en |
| dc.subject | click reaction | en |
| dc.subject | arylboronic ester | en |
| dc.subject | mesoporous silica nanoparticle | en |
| dc.title | 針對過氧化氫來發展分子工具之研究 | zh_TW |
| dc.title | Study on the Development of H2O2-Responsive Molecular Tools | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 簡敦誠;李文山 | zh_TW |
| dc.contributor.oralexamcommittee | Tun-Cheng Chien;Wen-Shan Li | en |
| dc.subject.keyword | 前驅藥,活性含氧物響應載體系統,苯硼酸酯,介孔二氧化矽納米粒子,阿黴素,β-拉帕?,點擊化學, | zh_TW |
| dc.subject.keyword | Prodrug,ROS-responsive carrier system,arylboronic ester,mesoporous silica nanoparticle,doxorubicin,β-lapachone,click reaction, | en |
| dc.relation.page | 115 | - |
| dc.identifier.doi | 10.6342/NTU201902805 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-08-14 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| dc.date.embargo-lift | 2029-12-31 | - |
| 顯示於系所單位： | 化學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-2.pdf 未授權公開取用 | 6.66 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。