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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 周涵怡(Han-Yi Chou) | |
| dc.contributor.author | Ta-Wei Chien | en |
| dc.contributor.author | 簡大為 | zh_TW |
| dc.date.accessioned | 2021-06-07T23:58:19Z | - |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-17 | |
| dc.identifier.citation | 1 L. Aagaard, and J. J. Rossi, 'Rnai Therapeutics: Principles, Prospects and Challenges', Advanced Drug Delivery Reviews, 59 (2007), 75-86.
2 A. A. Ahmed, Z. Lu, N. B. Jennings, D. Etemadmoghadam, L. Capalbo, R. O. Jacamo, N. Barbosa-Morais, X. F. Le, P. Vivas-Mejia, G. Lopez-Berestein, G. Grandjean, G. Bartholomeusz, W. Liao, M. Andreeff, D. Bowtell, D. M. Glover, A. K. Sood, R. C. Bast, and Australian Ovarian Canc Study Grp, 'Sik2 Is a Centrosome Kinase Required for Bipolar Mitotic Spindle Formation That Provides a Potential Target for Therapy in Ovarian Cancer', Cancer Cell, 18 (2010), 109-21. 3 A. Alhaddad, Adam, M.-P., Botsoa, J., Dantelle, G., Perruchas, S., Gacoin, T., Mansuy, C., Lavielle, S., Malvy, C., Treussart, F. and Bertrand, J.-R., 'Nanodiamond as a Vector for Sirna Delivery to Ewing Sarcoma Cells.', Small, 7 (2011), 3087-95. 4 S. Barathmanikanth, K. Kalishwaralal, M. Sriram, S. R. Pandian, H. S. Youn, S. Eom, and S. Gurunathan, 'Anti-Oxidant Effect of Gold Nanoparticles Restrains Hyperglycemic Conditions in Diabetic Mice', J Nanobiotechnology, 8 (2010), 16. 5 G. M. Barton, and R. Medzhitov, 'Retroviral Delivery of Small Interfering Rna into Primary Cells', Proceedings of the National Academy of Sciences of the United States of America, 99 (2002), 14943-45. 6 W. J. Blot, J. K. Mclaughlin, D. M. Winn, D. F. Austin, R. S. Greenberg, S. Prestonmartin, L. Bernstein, J. B. Schoenberg, A. Stemhagen, and J. F. Fraumeni, 'Smoking and Drinking in Relation to Oral and Pharyngeal Cancer', Cancer Research, 48 (1988), 3282-87. 7 P. R. Brink, R. B. Robinson, M. R. Rosen, and I. S. Cohen, 'In Vivo Cellular Delivery of Sirna', Idrugs, 13 (2010), 383-87. 8 Y. R. Chang, H. Y. Lee, K. Chen, C. C. Chang, D. S. Tsai, C. C. Fu, T. S. Lim, Y. K. Tzeng, C. Y. Fang, C. C. Han, H. C. Chang, and W. Fann, 'Mass Production and Dynamic Imaging of Fluorescent Nanodiamonds', Nature Nanotechnology, 3 (2008), 284-88. 9 W. Choi, C. Fang-Yen, K. Badizadegan, S. Oh, N. Lue, R. R. Dasari, and M. S. Feld, 'Tomographic Phase Microscopy', Nat Methods, 4 (2007), 717-19. 10 C. L. Curl, C. J. Bellair, T. Harris, B. E. Allman, P. J. Harris, A. G. Stewart, A. Roberts, K. A. Nugent, and L. M. D. Delbridge, 'Refractive Index Measurement in Viable Cells Using Quantitative Phase-Amplitude Microscopy and Confocal Microscopy', Cytometry Part A, 65A (2005), 88-92. 11 V. V. Danilenko, 'On the History of the Discovery of Nanodiamond Synthesis', Physics of the Solid State, 46 (2004), 595-99. 12 W. H. De Jong, and P. J. A. Borm, 'Drug Delivery and Nanoparticles: Applications and Hazards', International Journal of Nanomedicine, 3 (2008), 133-49. 13 G. R. Devi, T. M. Beer, C. L. Corless, V. Arora, D. L. Weller, and P. L. Iversen, 'In Vivo Bioavailability and Pharmacokinetics of a C-Myc Antisense Phosphorodiamidate Morpholino Oligomer, Avi-4126, in Solid Tumors', Clinical Cancer Research, 11 (2005), 3930-8. 14 S. M. Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, and T. Tuschl, 'Duplexes of 21-Nucleotide Rnas Mediate Rna Interference in Cultured Mammalian Cells', Nature, 411 (2001), 494-98. 15 S. S. Forootan, Z. Z. Bao, F. S. Forootan, L. Kamalian, Y. Zhang, A. Bee, C. S. Foster, and Y. Q. Ke, 'Atelocollagen-Delivered Sirna Targeting the Fabp5 Gene as an Experimental Therapy for Prostate Cancer in Mouse Xenografts', International Journal of Oncology, 36 (2010), 69-76. 16 Timothy M. Frayling, Nicholas J. Timpson, Michael N. Weedon, Eleftheria Zeggini, Rachel M. Freathy, Cecilia M. Lindgren, John R. B. Perry, Katherine S. Elliott, Hana Lango, Nigel W. Rayner, Beverley Shields, Lorna W. Harries, Jeffrey C. Barrett, Sian Ellard, Christopher J. Groves, Bridget Knight, Ann-Marie Patch, Andrew R. Ness, Shah Ebrahim, Debbie A. Lawlor, Susan M. Ring, Yoav Ben-Shlomo, Marjo-Riitta Jarvelin, Ulla Sovio, Amanda J. Bennett, David Melzer, Luigi Ferrucci, Ruth J. F. Loos, Ines Barroso, Nicholas J. Wareham, Fredrik Karpe, Katharine R. Owen, Lon R. Cardon, Mark Walker, Graham A. Hitman, Colin N. A. Palmer, Alex S. F. Doney, Andrew D. Morris, George Davey Smith, The Wellcome Trust Case Control Consortium, Andrew T. Hattersley, and Mark I. McCarthy, 'A Common Variant in the Fto Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity', Science, 316 (2007), 889-94. 17 C. C. Fu, H. Y. Lee, K. Chen, T. S. Lim, H. Y. Wu, P. K. Lin, P. K. Wei, P. H. Tsao, H. C. Chang, and W. Fann, 'Characterization and Application of Single Fluorescent Nanodiamonds as Cellular Biomarkers', Proc Natl Acad Sci U S A, 104 (2007), 727-32. 18 Pawan Gulati, Man Ka Cheung, Robin Antrobus, Chris D. Church, Heather P. Harding, Yi-Chun Loraine Tung, Debra Rimmington, Marcella Ma, David Ron, Paul J. Lehner, Frances M. Ashcroft, Roger D. Cox, Anthony P. Coll, Stephen O’Rahilly, and Giles S. H. Yeo, 'Role for the Obesity-Related Fto Gene in the Cellular Sensing of Amino Acids', Proceedings of the National Academy of Sciences (2013). 19 S. T. Guo, and L. Huang, 'Nanoparticles Escaping Res and Endosome: Challenges for Sirna Delivery for Cancer Therapy', Journal of Nanomaterials (2011). 20 S. Hallaj-Nezhadi, F. Lotfipour, and C. R. Dass, 'Delivery of Nanoparticulate Drug Delivery Systems Via the Intravenous Route for Cancer Gene Therapy', Pharmazie, 65 (2010), 855-59. 21 W. C. Hsu, J. W. Su, C. C. Chang, and K. B. Sung, 'Investigating the Backscattering Characteristics of Individual Normal and Cancerous Cells Based on Experimentally Determined Three-Dimensional Refractive Index Distributions', (2012). 22 Y. Y. Hui, C. L. Cheng, and H. C. Chang, 'Nanodiamonds for Optical Bioimaging', Journal of Physics D-Applied Physics, 43 (2010). 23 S. M. Hussain, and J. J. Schlager, 'Safety Evaluation of Silver Nanoparticles: Inhalation Model for Chronic Exposure', Toxicol Sci, 108 (2009), 223-4. 24 Y. C. Ko, Y. L. Huang, C. H. Lee, M. J. Chen, L. M. Lin, and C. C. Tsai, 'Betel Quid Chewing, Cigarette-Smoking and Alcohol-Consumption Related to Oral-Cancer in Taiwan', Journal of Oral Pathology & Medicine, 24 (1995), 450-53. 25 S. D. Li, S. Chono, and L. Huang, 'Efficient Oncogene Silencing and Metastasis Inhibition Via Systemic Delivery of Sirna', Molecular Therapy, 16 (2008), 942-46. 26 D. Mahl, J. Diendorf, W. Meyer-Zaika, and M. Epple, 'Possibilities and Limitations of Different Analytical Methods for the Size Determination of a Bimodal Dispersion of Metallic Nanoparticles', Colloids and Surfaces a-Physicochemical and Engineering Aspects, 377 (2011), 386-92. 27 V. N. Mochalin, O. Shenderova, D. Ho, and Y. Gogotsi, 'The Properties and Applications of Nanodiamonds', Nature Nanotechnology, 7 (2012), 11-23. 28 K. L. Mossman, 'Quantitative Radiation Dose-Response Relationships for Normal Tissues in Man. Ii. Response of the Salivary Glands During Radiotherapy', Radiat Res, 95 (1983), 392-8. 29 V. A. Murrah, and J. G. Batsakis, 'Proliferative Verrucous Leukoplakia and Verrucous Hyperplasia', Annals of Otology Rhinology and Laryngology, 103 (1994), 660-63. 30 M. Nakayama, and T. Okano, '[Drug Delivery Systems Using Nano-Sized Drug Carriers]', Gan To Kagaku Ryoho, 32 (2005), 935-40. 31 J. J. Pindborg, P. R. Murti, R. B. Bhonsle, P. C. Gupta, D. K. Daftary, and F. S. Mehta, 'Oral Submucous Fibrosis as a Precancerous Condition', Scandinavian Journal of Dental Research, 92 (1984), 224-29. 32 A. M. Schrand, L. Dai, J. J. Schlager, S. M. Hussain, and E. Osawa, 'Differential Biocompatibility of Carbon Nanotubes and Nanodiamonds', Diamond and Related Materials, 16 (2007), 2118-23. 33 C. X. Shen, A. K. Buck, X. W. Liu, M. Winkler, and S. N. Reske, 'Gene Silencing by Adenovirus-Delivered Sirna', Febs Letters, 539 (2003), 111-14. 34 R. Singh, and J. W. Lillard, 'Nanoparticle-Based Targeted Drug Delivery', Experimental and Molecular Pathology, 86 (2009), 215-23. 35 S. A. Stacker, M. G. Achen, L. Jussila, M. E. Baldwin, and K. Alitalo, 'Lymphangiogenesis and Cancer Metastasis', Nature Reviews Cancer, 2 (2002), 573-83. 36 J. W. Su, W. C. Hsu, C. Y. Chou, C. H. Chang, and K. B. Sung, 'Digital Holographic Microtomography for High-Resolution Refractive Index Mapping of Live Cells', J Biophotonics, 6 (2013), 416-24. 37 Y. Takei, K. Kadomatsu, Y. Yuzawa, S. Matsuo, and T. Muramatsu, 'A Small Interfering Rna Targeting Vascular Endothelial Growth Factor as Cancer Therapeutics', Cancer Research, 64 (2004), 3365-70. 38 F. Takeshita, and T. Ochiya, 'Therapeutic Potential of Rna Interference against Cancer', Cancer Science, 97 (2006), 689-96. 39 F. Turati, W. Garavello, I. Tramacere, C. Pelucchi, C. Galeone, V. Bagnardi, G. Corrao, F. Islami, V. Fedirko, P. Boffetta, C. La Vecchia, and E. Negri, 'A Meta-Analysis of Alcohol Drinking and Oral and Pharyngeal Cancers: Results from Subgroup Analyses', Alcohol and Alcoholism, 48 (2013), 107-18. 40 T. Waldman, Y. Zhang, L. Dillehay, J. Yu, K. Kinzler, B. Vogelstein, and J. Williams, 'Cell-Cycle Arrest Versus Cell Death in Cancer Therapy', Nat Med, 3 (1997), 1034-6. 41 S. Wallerstedt, R. Olsson, and J. Waldenstrom, 'The Diagnostic Significance of a High Asat/Alat (Got/Gpt) Ratio in Patients with Very High Serum Aminotransferase Levels', Acta Medica Scandinavica, 195 (1974), 227-29. 42 G. Walsberg, and B. Wolf, 'Variation in the Respiratory Quotient of Birds and Implications for Indirect Calorimetry Using Measurements of Carbon Dioxide Production', J Exp Biol, 198 (1995), 213-9. 43 K. Wang, Z. C. Gao, G. Gao, Y. Wo, Y. X. Wang, G. X. Shen, and D. X. Cui, 'Systematic Safety Evaluation on Photoluminescent Carbon Dots', Nanoscale Research Letters, 8 (2013). 44 Ming Wang, and Andrei L. Gartel, The Suppression of Foxm1 and Its Targets in Breast Cancer Xenograft Tumors by Sirna. Vol. 2, 2011 (2011). 45 K. A. Whitehead, R. Langer, and D. G. Anderson, 'Knocking Down Barriers: Advances in Sirna Delivery', Nature Reviews Drug Discovery, 8 (2009), 129-38. 46 N. Yagi, I. Manabe, T. Tottori, A. Ishihara, F. Ogata, J. H. Kim, S. Nishimura, K. Fujiu, Y. Oishi, K. Itaka, Y. Kato, M. Yamauchi, and R. Nagai, 'A Nanoparticle System Specifically Designed to Deliver Short Interfering Rna Inhibits Tumor Growth in Vivo', Cancer Research, 69 (2009), 6531-38. 47 J. Yano, K. Hirabayashi, S. Nakagawa, T. Yamaguchi, M. Nogawa, I. Kashimori, H. Naito, H. Kitagawa, K. Ishiyama, T. Ohgi, and T. Irimura, 'Antitumor Activity of Small Interfering Rna/Cationic Liposome Complex in Mouse Models of Cancer', Clinical Cancer Research, 10 (2004), 7721-26. 48 Y. Yuan, Y. W. Chen, J. H. Lui, H. F. Wang, and Y. F. Liu, 'Biodistribution and Fate of Nanodiamonds in Vivo', Diamond and Related Materials, 18 (2009), 95-100. 49 C. Zhou, M. Long, Y. P. Qin, X. K. Sun, and J. Zheng, 'Luminescent Gold Nanoparticles with Efficient Renal Clearance', Angewandte Chemie-International Edition, 50 (2011), 3168-72. 50 Y. Zhu, J. Li, W. X. Li, Y. Zhang, X. F. Yang, N. Chen, Y. H. Sun, Y. Zhao, C. H. Fan, and Q. Huang, 'The Biocompatibility of Nanodiamonds and Their Application in Drug Delivery Systems', Theranostics, 2 (2012), 302-12. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17145 | - |
| dc.description.abstract | 由本實驗室先前的研究已證實出奈米鑽石在協助短干擾核醣核酸進入腫瘤細胞抑制目標基因表現的過程中具有相當大的成效，因此，在發展以此基因療法進入活體並治療癌症的過程中，去驗證奈米鑽石是否在活體內也能夠促進短干擾核醣核酸的傳遞並抑制目標基因是必要的。另一方面，奈米鑽石身為一個外來載體，其未來應用在活體內癌症治療上的生物相容性之疑慮仍然存在；因此，我們必須進行奈米鑽石在活體內之生物相容性測試。在本實驗中，我們利用異種移植腫瘤模式，分析奈米鑽石攜帶短干擾核醣核酸之傳遞效率：藉由比較基因抑制程度、抑制速率、抑制間期長短、腫瘤生長趨勢、及鑽石劑量效應，我們證實出在活體內奈米鑽石的確能夠促進目標基因的專一性抑制。就生物相容性測試方面，我們將不同劑量之奈米鑽石由尾靜脈及腹腔注入活體內，再利用組織切片和血液生化測試來觀察指標器官功能指數是否受到影響；同時搭配基礎生理量測監控，我們發現即使在最高劑量之奈米鑽石實驗組別與對照組之間仍沒有顯著差異，顯示奈米鑽石對活體內主要器官功能及形態上是無害的。最後為了發展未來奈米鑽石在活體內追蹤的可行性，我們應用奈米鑽石獨特的高折射率，利用斷層相位顯微鏡記錄相位變化的方式重建出細胞與奈米鑽石的影像，成功辨別出細胞內奈米鑽石的三維分布，對未來於活體內追蹤奈米鑽石的方式建立新的里程碑。綜合以上結果，我們相信奈米鑽石是個具有高潛力之可追蹤藥物載體，期望本研究在未來癌症治療上能帶給人民福祉。 | zh_TW |
| dc.description.abstract | Previous studies from our laboratory have demonstrated that nanodiamonds (NDs) can promote delivery of siRNA into cancer cells to enhance target gene suppression. In order to develop ND-mediated delivery into clinically applicable gene therapy for cancer, it is necessary to verify its silencing efficiency in vivo. In this study, we use tumor xenograft model to analyze the delivery efficiency of ND-carried siRNA complexes, by comparing the kinetics of target gene suppression level and its effect on tumor growth. Our results indicate that NDs can greatly promote the delivery of siRNA efficiency in vivo. On the other hand, despites of the high bio-inertness of ND, it still remains to be tested whether NDs display good in vivo biocompatibility under invasive administration scheme. Toward this end, we examined the physiological and pathological responses of mice after administration of ND by intravenous and intraperitoneal injection, and observed no significant abnormality in the ND treated mice. Taken these together, our results suggest that ND can be an excellent siRNA delivery vector for the treatment of cancer, and thus prompt us to develop a practical method for its tracking in vivo. We explored the high refractive index of NDs for imaging by tomographic phase microscopy, and identified intracellular NDs in 3 dimensions. Combining the good delivery efficiency, high biocompatibility and traceable characteristics, we believe that ND promises high potentials as drug vector and might bring great welfare in cancer therapy in the future. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T23:58:19Z (GMT). No. of bitstreams: 1 ntu-102-R00450016-1.pdf: 2682968 bytes, checksum: 012ee3f272bedbe447c31e931b8c584b (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii ABSTRACT iii CONTENTS iv Chapter 1 Introduction 1 1.1 Oral cancer 1 1.2 Cancer therapy 1 1.3 Current cancer therapy for oral cancer 2 1.4 Potential cancer therapy for oral cancer 2 1.5 siRNA delivery barrier during transfection 3 1.6 Nano-sized carriers for drug delivery 3 1.7 Nanodiamond 4 1.8 Concerning the result after delivery 5 1.9 Novel application for tracking ND carrier 6 1.10 Tomographic phase microscopy 7 Chapter 2 Materials and Methods 8 2.1 Nanodiamonds 8 2.2 Cell culture condition 8 2.3 ND preparing process 8 2.4 siRNA preparation 9 2.5 siRNA sequence decision 9 2.6 Luciferin preparation 9 2.7 Implantation of xenograft 10 2.8 Kinetics of anti-luciferase siRNA doses with or w/o nd in xenograft 10 2.9 Effect of different doses ND helping fixed amount siRNA transportation in xenograft 11 2.10 Tumor volume measurement 11 2.11 Biosafety evaluation of ND in vivo 11 2.12 Clinical biochemistry measurement – liver function index (GPT & GOT) 12 2.13 Clinical biochemistry measurement – renel function (Blood Urea Nitrogen) 12 2.14 Respiratory quotient 12 2.15 Fasting glucose and mice body weight 13 2.16 Histological examination 13 2.17 TPM sample preparation 14 2.18 Tomographic phase microscope 14 Chapter 3 Result 15 3.1 Investigation of ND-carried siRNA against tumor growth-independent gene expression in vivo 15 3.2 Investigating the relationship between ND doses and silencing performance in vivo 16 3.3 The Biosafety evaluation of nanodiamond in vivo 17 3.3.1 Body weight and fasting glucose 18 3.3.2 Respiratory quotient 18 3.3.3 Liver function index (GPT, GOT) 18 3.3.4 Blood urea nitrogen concentration (BUN) 19 3.3.5 Major organs pathology 19 3.4 Quantify the refractive index of cellular structure 20 3.5 Investigating nanodiamond distribution in cancer cell by cut 20 3.6 Investigating nanodiamond distribution by tomographic scanning 21 Chapter 4 Discussion 22 ND displays a comprehensive upgradation in siRNA delivery kinetics. 22 siRNA efficiency were ND dose dependent. 23 Either intravenous or intraperitoneal injection of ND behaves high biosafety evaluation in animal model. 24 The intracellular ND detection due to refractive index can be achieved. 25 Chapter 5 Conclusion 27 Chapter 6 Future Work 28 Investigation of ND-carried siRNA silencing ability against tumor growth. 28 Monitoring living cells engulfing ND by TPM 28 Detecting engulfed ND by TPM in vivo. 28 Chapter 7 Reference 30 Chapter 8 Table 34 Chapter 9 Figures and Legends 36 Chapter 10 Appendix 61 | |
| dc.language.iso | en | |
| dc.subject | 活體追蹤 | zh_TW |
| dc.subject | 奈米鑽石 | zh_TW |
| dc.subject | 短干擾核醣核酸傳遞效率 | zh_TW |
| dc.subject | 生物相容性 | zh_TW |
| dc.subject | nanodiamond | en |
| dc.subject | in vivo tracing | en |
| dc.subject | biocompatibility | en |
| dc.subject | siRNA delivery | en |
| dc.title | 探討以奈米鑽石於活體內傳送雙股核醣核酸之效率與其生物耐受性及追蹤方式 | zh_TW |
| dc.title | Delivery, Biosafety and Tracing of Nanodiamond-dsRNA Complexes in vivo | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李伯訓(Bor-Shiunn Lee),宋孔彬(Kung-Bin Sung) | |
| dc.subject.keyword | 奈米鑽石,短干擾核醣核酸傳遞效率,生物相容性,活體追蹤, | zh_TW |
| dc.subject.keyword | nanodiamond,siRNA delivery,biocompatibility,in vivo tracing, | en |
| dc.relation.page | 63 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2013-08-17 | |
| dc.contributor.author-college | 牙醫專業學院 | zh_TW |
| dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
| Appears in Collections: | 口腔生物科學研究所 | |
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| ntu-102-1.pdf Restricted Access | 2.62 MB | Adobe PDF |
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