博碩士論文 103324049 詳細資訊




以作者查詢圖書館館藏 以作者查詢臺灣博碩士 以作者查詢全國書目 勘誤回報 、線上人數:28 、訪客IP:54.159.64.172
姓名 顏欣柔(SHIN-ROU YAN)  查詢紙本館藏   畢業系所 化學工程與材料工程學系
論文名稱 利用寡聚精胺酸促進去氧寡核苷酸輸送
(The Use of Oligoarginine for Oligodeoxynucleotide Delivery)
檔案 [Endnote RIS 格式]    [Bibtex 格式]    至系統瀏覽論文 ( 永不開放)
摘要(中) 本研究中以聚精胺酸R9作為基礎,利用各種不同方法形成不同的載體模式來探討對去氧寡核苷酸(ODN)的輸送效果,這些載體模式包含PEI/ODN、R9/ODN、R9C/ODN(二聚體)、PEI10/R9/ODN(三成分)、PEI10/R9C/ODN(三成分)與PEI-R9C/ODN(接枝)六種。在表面電位與粒子大小方面,不同形式載體與ODN依照的各種氮磷(N/P)比混合,可發現在PEI、R9C和PEI-R9C與ODN可藉靜電力形成複合粒子,且表面電位亦隨劑量增加,相對的R9僅能吸附於ODN,減低ODN斥力並造成ODN聚集。而所有粒子大小皆在巨噬細胞的巨噬範圍裡(0.3~10µm)。關於載體的包覆率,除了R9載體之外,其他載體皆有隨載體劑量而提升,能使複合物更穩定。接下來,在螢光顯微鏡中,除R9/ODN之外,其他皆能使複合物進入細胞內,甚至優於PEI/ODN的控制組。還有,在雷射共軛焦顯微鏡結果顯示在有R9C參與的載體系統中,ODN皆能成功從核內體逃脫進入細胞質。細胞毒性測試證實各載體並無明顯毒性出現。最後為了確認是否能應用至基因沉默上,我們進行TNF-α的蛋白質的抑制實驗,並利用不同實驗條件證實穿膜與胞吞的結果,結果指出R9C不論是單獨使用或配合PEI,均可直接穿膜以抑制TNF-α的表現。相較之下PEI所參與的輸送方式是藉由包吞進入細胞,因此ODN藥效的時間上較為延後。綜觀而言,PEI10/R9C/ODN可兼具兩種輸送的途徑優勢,因此得以延長基因沉默的療效,這將有助於臨床上的應用。
摘要(英) Oligoarginine, R9, is investigated of its potential on oligodeoxynucleotide (ODN) delivery. Cysteine modified R9 (R9C) and polyethylenimine (PEI) were also co-administrated so that there were 6 different delivery modes in this study, including PEI/ODN, R9/ODN, R9C/ODN, PEI-R9C/ODN (conjugates), PEI10/R9/ODN, and PEI/R9C/ODN. These carriers were complexed with ODN in different N/P ratios. Zeta potentials of formed nanoparticles increased with increasing carrier molecules. In contrast, R9 can only adsorb onto ODN without nanoparticle formation, which resulted in reducing repulse forces and leading ODN aggregation. However, the formed particle-sizes in all groups were ranged between 0.3 to 10µm, which were suitable for macrophage uptake. About the encapsulation, all carriers effectively loaded ODN except R9, and the loading efficiency increased with increasing carriers. The fluorescent microscopy illustrated that that all groups can deliver ODN into cells except the R9/ODN group. The confocal microscopy results suggested that R9C involving carrier systems (R9C/ODN, PEI10/R9C/ODN, and PEI-R9/ODN) can even facilitate endosomal escape. The biocompatibility assay suggested all carriers did not elicit severe cytotoxicity. Finally, we applied these systems to deliver anti-TNF-α ODN to evaluate their gene silence efficiencies. The results indicated that R9C/ODN and PEI10/R9C/ODN can inhibit TNF-α expression through transmembrane pathway. In contrast, PEI/ODN and PEI10/R9C/ODN can be uptake through endocytosis. Because PEI10/R9C/ODN can deliver ODN by both direct penetration and endocytosis pathways, the period of gene silence can be elongated, which should be an optimal delivery mode for clinical application.
關鍵字(中) ★ 精胺酸
★ 聚乙烯亞胺
★ 去氧寡核苷酸
關鍵字(英) ★ arginine
★ polyethylenimine
★ oligodeoxynucleotide
論文目次 摘要 I
Abstract II
誌謝 III
目錄 V
圖目錄 VIII
表目錄 X
第一章 緒論 1
1-1 研究背景 1
1-2 研究動機 2
第二章 文獻回顧 3
2-1免疫反應 3
2-1-1免疫系統 3
2-1-2免疫失調 3
2-1-2-1腫瘤壞死因子(Tumor necrosis factor α) 4
2-1-2-2免疫失調疾病與治療 4
2-2基因治療 5
2-2-1用於基因沉默之基因抑制藥物 5
2-3基因載體 9
2-3-1病毒型載體 9
2-3-1-1反轉錄病毒 9
2-3-1-2腺病毒 10
2-3-1-3腺聯病毒 11
2-3-2非病毒型載體 11
2-3-2-1針頭注射 12
2-3-2-2基因槍 12
2-3-2-3電穿孔 13
2-3-2-4超聲波穿孔 13
2-3-2-5脂質體 13
2-3-2-6陽離子型高分子 15
2-4胜肽 17
2-4-1穿膜胜肽 17
2-4-2 穿膜胜肽進入細胞機制 19
2-4-3胜肽應用於寡核苷酸輸送 20
2-5聚乙烯亞胺(PEI) 22
2-5-1質子海綿效應 22
2-6胜肽與PEI對基因的輸送方法 24
2-6-1胜肽修飾PEI 24
2-6-2三成分摻混對基因的輸送 24
第三章 材料與方法 26
3-1 材料 26
3-1-1 合成 26
3-1-2 細胞培養 27
3-2儀器 30
3-3實驗方法 32
3-3-1溶液配製 32
3-3-2 HPLC與MASS分析測試 35
3-3-3合成 35
3-3-3-1PEI-Peptide conjugation 35
3-3-4NPS製備 37
3-3-5 粒徑大小與表面電位(DLS) 39
3-3-6 接枝率分析 40
3-3-6-1 TBNSA 40
3-3-7包覆率實驗 42
3-3-7-1製膠(1% agarose膠片) 42
3-3-7-2跑膠與照膠 42
3-3-7-3螢光標定法 43
3-3-8細胞轉染實驗 45
3-3-8-1細胞存活率(MTT) 45
3-3-8-2螢光顯微鏡(Fluorescent microscope) 45
3-3-8-3雷射共軛焦顯微鏡(Confocal) 45
3-3-8-4蛋白質抑制實驗 46
3-3-8-4-1轉染 46
3-3-8-4-2 Lipopolysaccharide(LPS)刺激TNFα產生 46
3-3-8-4-3 MTT Normalize 47
3-3-8-4-4ELISA蛋白質分析 47
第四章 結果與討論 48
4-1 材料分析 48
4-1-1 HPLC 48
4-1-2質譜儀 49
4-2奈米粒子物性鑑定 52
4-2-1TNBSA分析交聯劑接枝率 52
4-2-2DTNB分析胜肽接枝率 52
4-2-3 表面電位 54
4-2-4 粒子大小 56
4-2-5粒子包覆率 59
4-3奈米粒子對細胞攝取的影響 63
4-3-1螢光顯微鏡分析細胞攝取量 63
4-3-2雷射共軛焦顯微鏡探討細胞攝取 68
4-4奈米粒子對細胞存活率之影響 72
4-5奈米粒子對蛋白質表現的影響 75
第五章 結論 84
第六章 參考文獻 86
參考文獻 [1] C. Papagoras, P. V. Voulgari, and A. A. Drosos, "Strategies after the failure of the first anti-tumor necrosis factor alpha agent in rheumatoid arthritis," Autoimmunity Reviews, vol. 9, pp. 574-582, 2010.
[2] Z. Huang, Z. Zhang, Y. Zha, J. Liu, Y. Jiang, Y. Yang, J. Shao, X. Sun, X. Cai, Y. Yin, J. Chen, L. Dong, and J. Zhang, "The effect of targeted delivery of anti-TNF-α oligonucleotide into CD169+ macrophages on disease progression in lupus-prone MRL/lpr mice," Biomaterials, vol. 33, pp. 7605-7612, 2012.
[3] J. Maria, S. Karin, R. Cecilia, M. Brian, K. Søren, N. D. Tomas, G. J. Thomas, and G. M. Jacob, "Amelioration of Psoriasis by Anti-TNF-α RNAi in the Xenograft Transplantation Model′," Molecular Therapy, vol. 17, pp. 1743-53, 2009.
[4] M. L. Moss, L. Sklair-Tavron, and R. Nudelman, "Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis," Nature Clinical Practice Rheumatology, vol. 4, pp. 300-309, 2008.
[5] R. C. Newton, K. A. Solomon, M. B. Covington, C. P. Decicco, P. J. Haley, S. M. Friedman, and K. Vaddi, "Biology of TACE inhibition," Annals of the Rheumatic Diseases, vol. 60, pp. III25-III32, 2001.
[6] P. D. Robbins and S. C. Ghivizzani, "Viral vectors for gene therapy," Pharmacology & Therapeutics, vol. 80, pp. 35-47, 1998.
[7] M. S. Al-Dosari and X. Gao, "Nonviral Gene Delivery: Principle, Limitations, and Recent Progress," Aaps Journal, vol. 11, pp. 671-681, 2009.
[8] J. L. Santos, D. Pandita, J. Rodrigues, A. P. Pego, P. L. Granja, and H. Tomas, "Non-Viral Gene Delivery to Mesenchymal Stem Cells: Methods, Strategies and Application in Bone Tissue Engineering and Regeneration," Current Gene Therapy, vol. 11, pp. 46-57, 2011.
[9] C. Ortiz Mellet, J. M. Garcia Fernandez, and J. M. Benito, "Cyclodextrin-based gene delivery systems," Chemical Society Reviews, vol. 40, pp. 1586–1608, 2011.
[10] M. A. Mintzer and E. E. Simanek, "Nonviral Vectors for Gene Delivery," Chemical Reviews, vol. 109, pp. 259-302, 2009.
[11] N. A. Alhakamy and C. J. Berkland, "Polyarginine molecular weight determines transfection efficiency of calcium condensed complexes," Mol Pharm, vol. 10, pp. 1940-8, 2013.
[12] S. Futaki, S. Goto, and Y. Sugiura, "Membrane permeability commonly shared among arginine-rich peptides," Molecular Recognition, vol. 16, pp. 260-264, 2003.
[13] S. Futaki, I. Nakase, A. Tadokoro, T. Takeuchi, and A. T. Jones, "Arginine-rich peptides and their internalization mechanisms," Biochemical Society Transactions, vol. 35, pp. 784-787, 2007.
[14] H. D. Herce, A. E. Garcia, J. Litt, R. S. Kane, P. Martin, N. Enrique, A. Rebolledo, and V. Milesi, "Arginine-Rich Peptides Destabilize the Plasma Membrane, Consistent with a Pore Formation Translocation Mechanism of Cell-Penetrating Peptides," Biophysical Journal, vol. 97, pp. 1917-1925, 2009.
[15] D. J. Mitchell, D. T. Kim, L. Steinman, C. G. Fathman, and J. B. Rothbard, "Polyarginine enters cells more efficiently than other polycationic homopolymers," J Pept Res, vol. 56, pp. 318-325, 2000.
[16] S. H. Lee, B. Castagner, and J. C. Leroux, "Is there a future for cell-penetrating peptides in oligonucleotide delivery?," Eur J Pharm Biopharm, vol. 85, pp. 5-11, 2013.
[17] R. Breslow, S. Belvedere, L. Gershell, and D. Leung, "The chelate effect in binding, catalysis, and chemotherapy," Pure and Applied Chemistry, vol. 72, pp. 333-342, 2000.
[18] W.-w. H. Chiao-chun Yeh, "The use of short peptides conjugated PEI for gene delivery application," 2013.
[19] W. W. Hu, Z. W. Lin, R. C. Ruaan, W. Y. Chen, S. L. C. Jin, and Y. Chang, "A novel application of indolicidin for gene delivery," International Journal of Pharmaceutics, vol. 456, pp. 293-300, 2013.
[20] A. K. Abbas, A. H. H. Lichtman, and S. Pillai, Basic Immunology: Functions and Disorders of the Immune System: Elsevier Health Sciences, 2012.
[21] M. Srirupa, R. H. John, and K. M. Tapan, "Role of TNFα in pulmonary pathophysiology," Respiratory Research, vol. 7, pp. 1-9, 2006.
[22] O. L. Carswell EA, Kassel RL, Green S, Fiore N, Williamson B, "Anendotoxin-induced serum factor that causes necrosis of tumors. ," Proceedings of the National Academy of Sciences of the United States of America, pp. 3666-3670., 1975.
[23] M. R. Shalaby, B. B. Aggarwal, E. Rinderknecht, L. P. Svedersky, B. S. Finkle, and M. A. Palladino, "Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors," The Journal of Immunology, vol. 135, pp. 2069-2073, 1985.
[24] S. J. V. Deventer, "Tumour necrosis factor and Crohn′s disease," Gut, vol. 40, pp. 443-448, 1997.
[25] 魏正宗, "抗腫瘤壞死因子製劑 (Anti-TNF)," 台灣醫界, vol. 第46卷, 2003.
[26] S. Tsiodras, G. Samonis, D. T. Boumpas, and D. P. Kontoyiannis, "Fungal infections complicating tumor necrosis factor alpha blockade therapy," Mayo Clinic Proceedings, vol. 83, pp. 181-194, 2008.
[27] D. o. Health, "Our inheritance, our future – realising the potential of genetics in the NHS. ," Genetics White Paper, vol. 1, p. 19, 2003.
[28] K. B. Kaufmann, H. Buning, A. Galy, A. Schambach, and M. Grez, "Gene therapy on the move," Embo Molecular Medicine, vol. 5, pp. 1642-1661, 2013.
[29] K. K. Jain, "Gene therapy," PHARMACOLOGY, vol. 2, 2007.
[30] L. K. Branski, C. T. Pereira, D. N. Herndon, and M. G. Jeschke, "Gene therapy in wound healing: present status and future directions," Gene Therapy, vol. 14, pp. 1-10, 2007.
[31] E. H. Kaji and J. M. Leiden, "Gene and stem cell therapies," Jama-Journal of the American Medical Association, vol. 285, pp. 545-550, 2001.
[32] E. Hood, "RNAi: what′s all the noise about gene silencing?," Environmental Health Perspectives, vol. 112, pp. A224-A229, 2004.
[33] G. W. Redberry, Gene silencing : new research. New York: Nova Science Publishers, 2006.
[34] V. K. Sharma, P. Rungta, and A. K. Prasad, "Nucleic acid therapeutics: basic concepts and recent developments," Rsc Advances, vol. 4, pp. 16618-16631, 2014.
[35] D. Grimm, "Small silencing RNAs: State-of-the-art," Advanced Drug Delivery Reviews, vol. 61, pp. 672-703, 2009.
[36] S. T. Crooke, "Progress in antisense technology," Annual Review of Medicine, vol. 55, pp. 61-95, 2004.
[37] N. Dias and C. A. Stein, "Antisense oligonucleotides: Basic concepts and mechanisms," Molecular Cancer Therapeutics, vol. 1, pp. 347-355, 2002.
[38] A. Forte, M. Cipollaro, A. Cascino, and U. Galderisi, "Small interfering RNAs and antisense oligonucleotides for treatment of neurological diseases," Current Drug Targets, vol. 6, pp. 21-29, 2005.
[39] 陳一村, "核糖核酸干擾術及其應用," biomedicine, vol. 1, 2008.
[40] 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, vol. 411, pp. 494-498, 2001.
[41] S. Parrish, J. Fleenor, S. Q. Xu, C. Mello, and A. Fire, "Functional anatomy of a dsRNA trigger: Differential requirement for the two trigger strands in RNA interference," Molecular Cell, vol. 6, pp. 1077-1087, 2000.
[42] P. D. Zamore, T. Tuschl, P. A. Sharp, and D. P. Bartel, "RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals," Cell, vol. 101, pp. 25-33, 2000.
[43] D. P. Bartel, "MicroRNAs: Genomics, biogenesis, mechanism, and function," Cell, vol. 116, pp. 281-297, 2004.
[44] N. I. Khatri, M. N. Rathi, D. P. Baradia, S. Trehan, and A. R. Misra, "In Vivo Delivery Aspects of miRNA, shRNA and siRNA," Critical Reviews in Therapeutic Drug Carrier Systems, vol. 29, pp. 487-527, 2012.
[45] M. D. Emine, "Antisense Oligodeoxynucleotide Technology:A Novel Tool for Gene Silencing in Higher Plants " 2012.
[46] A. L. Jackson, J. Burchard, J. Schelter, B. N. Chau, M. Cleary, L. Lim, and P. S. Linsley, "Widespread siRNA "off-target′′ transcript silencing mediated by seed region sequence complementarity," Rna-a Publication of the Rna Society, vol. 12, pp. 1179-1187, 2006.
[47] J. Wang, Z. Lu, M. G. Wientjes, and J. L. S. Au, "Delivery of siRNA Therapeutics: Barriers and Carriers," Aaps Journal, vol. 12, pp. 492-503, 2010.
[48] L. Dong, S. H. Xia, Y. Luo, H. J. Diao, J. Zhang, J. N. Chen, and J. F. Zhang, "Targeting delivery oligonucleotide into macrophages by cationic polysaccharide from Bletilla striata successfully inhibited the expression of TNF-alpha," Journal of Controlled Release, vol. 134, pp. 214-220, 2009.
[49] J. Kurreck, "Antisense technologies. Improvement through novel chemical modifications," Eur J Biochem, vol. 270, pp. 1628-1644, 2003.
[50] G. Galietta, A. Loizzo, S. Loizzo, G. Trombetta, S. Spanipinato, G. Campana, A. Capasso, M. Palermo, I. Guarino, and F. Franconi, "Administration of antisense oligonucleotide against pro-opiomelanocortin prevents enduring hormonal alterations induced by neonatal handling in male mice," European Journal of Pharmacology, vol. 550, pp. 180-185, 2006.
[51] T. Blessing, J. S. Remy, and J. P. Behr, "Monomolecular collapse of plasmid DNA into stable virus-like particles," Proceedings of the National Academy of Sciences of the United States of America, vol. 95, pp. 1427-1431, 1998.
[52] D. Bouard, N. Alazard-Dany, and F. L. Cosset, "Viral vectors: from virology to transgene expression," British Journal of Pharmacology, vol. 157, pp. 153-165, 2009.
[53] A. D. Miller, D. G. Miller, J. V. Garcia, and C. M. Lynch, "Use of retroviral vectors for gene transfer and expression," Methods in Enzymology, vol. 217, pp. 581-599, 1993.
[54] E. Tomlinson and A. P. Rolland, "Controllable gene therapy - Pharmaceutics of non-viral gene delivery systems," Journal of Controlled Release, vol. 39, pp. 357-372, 1996.
[55] P. O. Eric, "Nucleic Acid Delivery: Lentiviral and Retroviral Vectors," Material Method, vol. 3, p. 174, 2013.
[56] T. C. He, S. B. Zhou, L. T. da Costa, J. Yu, K. W. Kinzler, and B. Vogelstein, "A simplified system for generating recombinant adenoviruses," Proceedings of the National Academy of Sciences of the United States of America, vol. 95, pp. 2509-2514, 1998.
[57] E. Wagner, M. J. Hewlett, D. C. Bloom, and D. Camerini, "Basic Virology," Blackwell Publishing, 2008.
[58] J. S. Richard, "Adeno-associated virus: integration at a specific chromosomal locus.," Curr. Opin. Genet., vol. 3, pp. 74–80, 1993.
[59] H. Buning, L. Perabo, O. Coutelle, S. Quadt-Humme, and M. Hallek, "Recent developments in adeno-associated virus vector technology," Journal of Gene Medicine, vol. 10, pp. 717-733, 2008.
[60] H. Yin, R. L. Kanasty, A. A. Eltoukhy, A. J. Vegas, J. R. Dorkin, and D. G. Anderson, "Non-viral vectors for gene-based therapy," Nature Reviews Genetics, vol. 15, pp. 541-555, 2014.
[61] W. E. Klein RM, Wu R, Sanford JC., "High-velocity microprojectiles for delivering nucleic acids into living cells. Biotechnology.," Biotechnology, vol. 24, pp. 384-6, 1992.
[62] M. Uchida, H. Natsume, D. Kobayashi, K. Sugibayashi, and Y. Morimoto, "Effects of particle size, helium gas pressure and microparticle dose on the plasma concentration of indomethacin after bombardment of indomethacin-loaded poly-L-lactic acid microspheres using a Helios (TM) gun system," Biological & Pharmaceutical Bulletin, vol. 25, pp. 690-693, 2002.
[63] N. Yang, J. Burkholder, B. Roberts, B. Martinell, and D. McCabe, "In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment," Genetics, vol. 87, pp. 9568-9572, 1990.
[64] A. V. Titomirov, S. Sukharev, and E. Kistanova, "In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA," Biochimica Et Biophysica Acta, vol. 1088, pp. 131-134, 1991.
[65] F. Andre and L. M. Mir, "DNA electrotransfer: its principles and an updated review of its therapeutic applications," Gene Therapy, vol. 11, pp. S33-S42, 2004.
[66] G. ter Haar, "Therapeutic applications of ultrasound," Progress in Biophysics & Molecular Biology, vol. 93, pp. 111-129, 2007.
[67] H. J. Kim, J. F. Greenleaf, R. R. Kinnick, J. T. Bronk, and M. E. Bolander, "Ultrasound-mediated transfection of mammalian cells," Human Gene Therapy, vol. 7, pp. 1339-1346, 1996.
[68] P. George, P. Demetrios, and J. V. William, "Chapter 4 Lipid Vesicles as Carriers for Introducing Biologically Active Materials into Cells," Methods in Cell Biology, vol. 14, pp. 33–71, 1976.
[69] C. T. de Ilarduya, Y. Sun, and N. Duezguenes, "Gene delivery by lipoplexes and polyplexes," European Journal of Pharmaceutical Sciences, vol. 40, pp. 159-170, 2010.
[70] J. H. Felgner, R. Kumar, C. N. Sridhar, C. J. Wheeler, Y. J. Tsai, R. Border, P. Ramsey, M. Martin, and P. L. Felgner, "Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations," Journal of Biological Chemistry, vol. 269, pp. 2550-2561, 1994.
[71] P. L. Felgner, Ringold, G. M., "Cationic liposome-mediated transfection," Nature, vol. 337, pp. 387-388, 1989.
[72] C. F. Bennett, M. Y. Chiang, H. D. Chan, J. E. E. Shoemaker, and C. K. Mirabelli, "Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides," Molecular Pharmacology, vol. 41, pp. 1023-1033, 1992.
[73] C. Y. Wang, Huang, L., "Highly efficient DNA delivery mediated by pH-sensitive immunoliposomes," Biochemistry, vol. 28, pp. 9508-9514, 1989.
[74] J. Y. Legendre and F. C. Szoka, "Delivery of plasmid DNA into mammalian cell lines using pH-sensitive liposomes: comparison with cationic liposomes," Pharmaceutical Research, vol. 9, pp. 1235-1242, 1992.
[75] X. H. Zhou and L. Huang, "DNA transfection mediated by cationic liposomes containing lipopolylysine: characterization and mechanism of action," Biochimica Et Biophysica Acta-Biomembranes, vol. 1189, pp. 195-203, 1994.
[76] Y. H. Xu and F. C. Szoka, "Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection," Biochemistry, vol. 35, pp. 5616-5623, 1996.
[77] T. B. Wyman, F. Nicol, O. Zelphati, P. V. Scaria, C. Plank, and F. C. J. Szoka, "Design, Synthesis, and Characterization of a Cationic Peptide That Binds to Nucleic Acids and Permeabilizes Bilayers," Biochemistry, vol. 36, pp. 3008-3017, 1996.
[78] E. Hellstrand, A. Nowacka, D. Topgaard, S. Linse, and E. Sparr, "Membrane Lipid Co-Aggregation with alpha-Synuclein Fibrils," Plos One, vol. 8, p. 10, 2013.
[79] A. V. Ulasov, Y. V. Khramtsov, G. A. Trusov, A. A. Rosenkranz, E. D. Sverdlov, and A. S. Sobolev, "Properties of PEI-based Polyplex Nanoparticles That Correlate With Their Transfection Efficacy," Molecular Therapy, vol. 19, pp. 103-112, 2011.
[80] D. T. Curiel, S. Agarwal, E. Wagner, and M. Cotten, "Adenovirus enhancement of transferrin-polylysine-mediated gene delivery," Proceedings of the National Academy of Sciences of the United States of America, vol. 88, pp. 8850-8854, 1991.
[81] L. Jin, X. Zeng, M. Liu, Y. Deng, and N. Y. He, "Current progress in gene delivery technology based on chemical methods and nano-carriers," Theranostics, vol. 4, pp. 240-255, 2014.
[82] Z. Pharma, "What are peptides."
Available from: dhttp://www.zealandpharma.com/research-and-development/key-zealand-peptide-competences/what-are-peptides
[83] M. Green and P. M. Loewenstein, "Autonomous functional domains of chemically synthesized human immunodeficiency virus tat activator protein," Cell, vol. 55, pp. 1179-1188, 1988.
[84] A. D. Frankel and C. O. Pabo, "Cellular uptake of the tat protein from human immunodeficiency virus," Cell, vol. 55, pp. 1189-1193, 1988.
[85] E. Vives, P. Brodin, and B. Lebleu, "A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus," Journal of Biological Chemistry, vol. 272, pp. 16010-16017, 1997.
[86] K. M. Wagstaff and D. A. Jans, "Protein transduction: Cell penetrating peptides and their therapeutic applications," Current Medicinal Chemistry, vol. 13, pp. 1371-1387, 2006.
[87] F. Madani, S. Lindberg, U. Langel, S. Futaki, and A. Gr¨slund, "Mechanisms of Cellular Uptake of Cell-Penetrating Peptides," Journal of Biophysics, vol. 2011, 2011.
[88] Y. W. Huang, H. J. Lee, L. M. Tolliver, and R. S. Aronstam, "Delivery of Nucleic Acids and Nanomaterials by Cell-Penetrating Peptides: Opportunities and Challenges," Biomed Research International, vol. 2015, p. 834079, 2015.
[89] J. Regberg, A. Srimanee, and Ü. Langel, "Applications of Cell-Penetrating Peptides for Tumor Targeting and Future Cancer Therapies," Pharmaceuticals, vol. 5, p. 991, 2012.
[90] W. Y. Li, Y. J. Liu, J. W. Du, K. F. Ren, and Y. X. Wang, "Cell penetrating peptide-based polyplexes shelled with polysaccharide to improve stability and gene transfection," Nanoscale, vol. 7, pp. 8476-8484, 2015.
[91] J. Hoyer and I. Neundorf, "Peptide Vectors for the Nonviral Delivery of Nucleic Acids," Accounts of Chemical Research, vol. 45, pp. 1048-1056, 2012.
[92] J. M. Gump and S. F. Dowdy, "TAT transduction: the molecular mechanism and therapeutic prospects," Trends in Molecular Medicine, vol. 13, pp. 443-448, 2007.
[93] B. R. Liu, Y.-w. Huang, J. G. Winiarz, H.-J. Chiang, and H.-J. Lee, "Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism," Biomaterials, vol. 32, pp. 3520-3537, 2011.
[94] S. Futaki, T. Suzuki, W. Ohashi, T. Yagami, S. Tanaka, K. Ueda, and Y. Sugiura, "Arginine-rich peptides - An abundant source of membrane-permeable peptides having potential as carriers for intracellular protein delivery," Journal of Biological Chemistry, vol. 276, pp. 5836-5840, 2001.
[95] J. L. Zaro and W. C. Shen, "Quantitative comparison of membrane transduction and endocytosis of oligopeptides," Biochemical and Biophysical Research Communications, vol. 307, pp. 241-247, 2003.
[96] A. F. Saleh, H. Aojula, Y. Arthanari, S. Offerman, M. Alkotaji, and A. Pluen, "Improved Tat-mediated plasmid DNA transfer by fusion to LK15 peptide," Journal of Controlled Release, vol. 143, pp. 233-242, 2010.
[97] F. Salomone, F. Cardarelli, M. Di Luca, C. Boccardi, R. Nifosi, G. Bardi, L. Di Bari, M. Serresi, and F. Beltram, "A novel chimeric cell-penetrating peptide with membrane-disruptive properties for efficient endosomal escape," J Control Release, vol. 163, pp. 293-303, 2012.
[98] Y. J. Lee, A. Erazo-Oliveras, and J. P. Pellois, "Delivery of Macromolecules into Live Cells by Simple Co-incubation with a Peptide," Chembiochem, vol. 11, pp. 325-330, 2010.
[99] L. K. Fei, L. Ren, J. L. Zaro, and W. C. Shen, "The influence of net charge and charge distribution on cellular uptake and cytosolic localization of arginine-rich peptides," Journal of Drug Targeting, vol. 19, pp. 675-680, 2011.
[100] S. Abes, J. J. Turner, G. D. Ivanova, D. Owen, D. Williams, A. Arzumanov, P. Clair, M. J. Gait, and B. Lebleu, "Efficient splicing correction by PNA conjugation to an R6-Penetratin delivery peptide (vol 35, pg 4495, 2007)," Nucleic Acids Research, vol. 35, pp. 7396-7396, 2007.
[101] S. Deshayes, K. Konate, A. Rydstrom, L. Crombez, C. Godefroy, P. E. Milhiet, A. Thomas, R. Brasseur, G. Aldrian, F. Heitz, M. A. Munoz-Morris, J. M. Devoisselle, and G. Divita, "Self-assembling peptide-based nanoparticles for siRNA delivery in primary cell lines," Small, vol. 8, pp. 2184-2188, 2012.
[102] J.-M. Crowet, L. Lins, S. Deshayes, G. Divita, M. Morris, R. Brasseur, and A. Thomas, "Modeling of non-covalent complexes of the cell-penetrating peptide CADY and its siRNA cargo," Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 1828, pp. 499-509, 2013.
[103] R. H. Mo, J. L. Zaro, and W. C. Shen, "Comparison of cationic and amphipathic cell penetrating peptides for siRNA delivery and efficacy," Mol Pharm, vol. 9, pp. 299-309, 2012.
[104] H. L. Amand, B. Norden, and K. Fant, "Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation," Biochemical and Biophysical Research Communications, vol. 418, pp. 469-474, 2012.
[105] M. Balakirev, G. Schoehn, and J. Chroboczek, "Lipoic acid-derived amphiphiles for redox-controlled DNA delivery," Chemistry & Biology, vol. 7, pp. 813-819, 2000.
[106] M. L. Read, K. H. Bremner, D. Oupicky, N. K. Green, P. F. Searle, and L. W. Seymour, "Vectors based on reducible polycations facilitate intracellular release of nucleic acids," Journal of Gene Medicine, vol. 5, pp. 232-245, 2003.
[107] O. Boussif, F. Lezoualch, M. A. Zanta, M. D. Mergny, D. Scherman, B. Demeneix, and J. P. Behr, "A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine.," Proceedings of the National Academy of Sciences of the United States of America, vol. 92, pp. 7297-7301, 1995.
[108] L. De Laporte, J. C. Rea, and L. D. Shea, "Design of modular non-viral gene therapy vectors," Biomaterials, vol. 27, pp. 947-954, 2006.
[109] D. Fischer, T. Bieber, Y. X. Li, H. P. Elsasser, and T. Kissel, "A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: Effect of molecular weight on transfection efficiency and cytotoxicity," Pharmaceutical Research, vol. 16, pp. 1273-1279, 1999.
[110] C. N. Lungu, M. V. Diudea, M. V. Putz, and I. P. Grudzinski, "Linear and Branched PEIs (Polyethylenimines) and Their Property Space," International Journal of Molecular Sciences, vol. 17, p. 12, 2016.
[111] Z. Y. Zhang and B. D. Smith, "High-generation polycationic dendrimers are unusually effective at disrupting anionic vesicles: Membrane bending model," Bioconjugate Chemistry, vol. 11, pp. 805-814, 2000.
[112] A. E. Nel, L. Madler, D. Velegol, T. Xia, E. M. V. Hoek, P. Somasundaran, F. Klaessig, V. Castranova, and M. Thompson, "Understanding biophysicochemical interactions at the nano-bio interface," Nature Materials, vol. 8, pp. 543-557, 2009.
[113] E. J. Kwon, S. Liong, and S. H. Pun, "A truncated HGP peptide sequence that retains endosomolytic activity and improves gene delivery efficiencies," Mol Pharm, vol. 7, pp. 1260-5, 2010.
[114] H. J. Lee, R. Namgung, W. J. Kim, J. I. Kim, and I.-K. Park, "Targeted delivery of microRNA-145 to metastatic breast cancer by peptide conjugated branched PEI gene carrier," Macromolecular Research, vol. 21, pp. 1201-1209, 2013.
[115] S. Yamano, J. Dai, S. Hanatani, K. Haku, T. Yamanaka, M. Ishioka, T. Takayama, C. Yuvienco, S. Khapli, A. M. Moursi, and J. K. Montclare, "Long-term efficient gene delivery using polyethylenimine with modified Tat peptide," Biomaterials, vol. 35, pp. 1705-1715, 2014.
[116] Y. M. Lee, D. Lee, J. Kim, H. Park, and W. J. Kim, "RPM peptide conjugated bioreducible polyethylenimine targeting invasive colon cancer," J Control Release, vol. 205, pp. 172-80, 2015.
[117] T. Zhang, X. Xue, D. He, and J. T. Hsieh, "A prostate cancer-targeted polyarginine-disulfide linked PEI nanocarrier for delivery of microRNA," Cancer Letters, vol. 365, pp. 156-165, 2015.
[118] J. S. Oh, M. Park, J. S. Kim, and J. H. Jang, "Enhanced Cellular Transfection by Ternary Non-Viral Gene Vectors Coupled with Adeno-Associated Virus-Derived Peptides," Macromolecular Bioscience, vol. 14, pp. 121-130, 2014.
[119] E. B. Getz, M. Xiao, T. Chakrabarty, R. Cooke, and P. R. Selvin, "A comparison between the sulfhydryl reductants tris(2-carboxyethyl)phosphine and dithiothreitol for use in protein biochemistry," Anal Biochem, vol. 273, pp. 73-80, 1999.
[120] Tania, "TCEP or DTT?," 2014.
Available from: http://sites.psu.edu/msproteomics/2014/05/30/tcep-or-dtt/
[121] P. Cayot and G. Tainturier, "The quantification of protein amino groups by the trinitrobenzenesulfonic acid method: a reexamination," Anal Biochem, vol. 249, pp. 184-200, 1997.
[122] Y. Kang, S. Semones, J. Smith, and M. Frodyma, "Bacillus amyloliquefaciens strain," ed: Google Patents, 2011.
[123] I. Yudovin-Farber, J. Golenser, N. Beyth, E. I. Weiss, and A. J. Domb, "Quaternary Ammonium Polyethyleneimine: Antibacterial Activity," Journal of Nanomaterials, 2010.
[124] Edgar, " Chemical reaction of Ellman′s reagent (5,5′-dithiobis-(2-nitrobenzoic acid) or DTNB) with a thiol," 2010.
Available from: http://sites.psu.edu/msproteomics/2014/05/30/tcep-or-dtt/
[125]X. J. Loh, T. C. Lee, Q. Dou, and G. R. Deen, "Utilising inorganic nanocarriers for gene delivery," Biomater Sci, vol. 4, pp. 70-86, 2016.
[126] R. Kircheis, L. Wightman, and E. Wagner, "Design and gene delivery activity of modified polyethylenimines," Advanced Drug Delivery Reviews, vol. 53, pp. 341-358, 2001.
[127] W. Zauner, N. A. Farrow, and A. M. Haines, "In vitro uptake of polystyrene microspheres: effect of particle size, cell line and cell density," J Control Release, vol. 71, pp. 39-51, 2001.
[128] T. R. Green, J. Fisher, M. Stone, B. M. Wroblewski, and E. Ingham, "Polyethylene particles of a ′critical size′ are necessary for the induction of cytokines by macrophages in vitro," Biomaterials, vol. 19, pp. 2297-302, 1998.
[129] S. P. Strand, S. Danielsen, B. E. Christensen, and K. M. Varum, "Influence of chitosan structure on the formation and stability of DNA-chitosan polyelectrolyte complexes," Biomacromolecules, vol. 6, pp. 3357-3366, 2005.
[130] N. Jain, V. Goldschmidt, S. Oncul, Y. Arntz, G. Duportail, Y. Mély, and A. Klymchenko, "Lactose-ornithine bolaamphiphiles for efficient gene delivery in vitro," International Journal of Pharmaceutics, vol. 423, pp. 392-400, 2012.
[131] Y. Liu, D. A. Peterson, H. Kimura, and D. Schubert, "Mechanism of Cellular 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) Reduction," Journal of Neurochemistry, vol. 69, pp. 581-593, 1997.
[132] F. Simeoni, M. C. Morris, F. Heitz, and G. Divita, "Insight into the mechanism of the peptide-based gene delivery system MPG: implications for delivery of siRNA into mammalian cells," Nucleic Acids Research, vol. 31, pp. 2717-2724, 2003.
[133] R. Pan, W. Xu, F. Yuan, D. Chu, Y. Ding, B. Chen, M. Jafari, Y. Yuan, and P. Chen, "A novel peptide for efficient siRNA delivery in vitro and therapeutics in vivo," Acta Biomaterialia, vol. 21, pp. 74-84, 2015.
[134] A. Anna, D. Catherine, D. Géraldine, L. C. Eric, M. Claude, T. François, and B. Jean-Rémi, "Influence of the Internalization Pathway on the Efficacy of siRNA Delivery by Cationic Fluorescent Nanodiamonds in the Ewing Sarcoma Cell Model," Plos One, vol. 7, p. e52207, 2012.
指導教授 胡威文(Wei-Wen Hu) 審核日期 2016-8-29
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題,請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407,或E-mail聯絡  - 隱私權政策聲明