博碩士論文 105324034 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:11 、訪客IP:44.192.94.177
姓名 劉宜旻(Yi-Min Liu)  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 Indolicidin之二聚體形式對輸送去氧寡核?酸的影響
(The Effect of Dimeric Form of Indolicidin-Derived Peptide for Oligodeoxynucleotide Delivery)
相關論文
★ 利用穿膜胜肽改善帶正電高分子之轉染效率★ 利用導電高分子聚吡咯為基材以電刺激促進幹細胞分化
★ 以電刺激增進骨髓基質細胞骨分化之最佳化探討★ 利用電場控制導電性高分子以進行基因於聚電解質多層膜的組裝
★ 以短鏈胜肽接枝聚乙烯亞胺來進行基因輸送應用之研究★ 電紡絲製備褐藻酸鈉/聚己內酯之奈米複合纖維進行原位轉染
★ 電場對於複合奈米絲進行原位基因傳送之影響★ 利用電場調控聚電解質多層膜的釋放 以應用於基因輸送
★ 發展載藥電紡聚乳酸/多壁奈米碳管/聚乙二醇纖維★ 利用寡聚精胺酸促進去氧寡核苷酸輸送
★ 利用聚己內酯/褐藻酸鈉之複合電紡絲擴增癌症幹細胞★ 以二元體形式之Indolicidin 應用於去氧寡核苷酸之輸送
★ Indolicidin之色胺酸殘基對於轉染效率的影響★ 搭建可提供電刺激與機械刺激之生物反應器
★ 硬脂基化的Indolicidin作為傳送質體去氧核 酸的非病毒載體★ 開發促進傷口癒合之複合敷料
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 ( 永不開放)
摘要(中) 許多文獻指出腫瘤壞死因子α ( tumor-necrosis factor-α , TNF-α)的過度表達與一些炎症疾病有關,因此在本篇研究中,我們利用基因輸送的方式期望能降低TNF-α的表現以應用在臨床上。Indolicidin(IL)是具有潛力的細胞穿膜胜?,但其高細胞毒性限制了其應用。因此本研究欲開發IL衍生?以輸送去氧寡核?酸(ODN),並探討二聚體的斷鍵與否對於基因輸送及沉默效果的影響。CIL胜?為IL的N端接上一個半胱胺酸(cysteine),HPLC和SDS-PAGE結果證實CIL能透過雙硫鍵形成二聚體。另外,我們亦設計一CIL二聚體的類似胜?,但將其半胱胺酸改成結構相似的絲胺酸(serine),並命名為S28。透過DLS和膠體電泳實驗可以發現CIL和S28不論是分子量或是正電荷個數均高於IL,因此能與ODN有效形成較穩定的複合物,且所形成的粒子大小都在巨噬細胞的吞噬範圍內。由螢光標定結果證實,CIL和S28均可提高細胞攝取率且促進內體逃脫。因此將其應用於TNF-α的基因沉默實驗,其結果顯示CIL和S28均比IL具有更佳的抑制效果。在生物適合性的部份,溶血實驗和MTT結果證實二聚體形式可降低IL所造成的膜擾動及細胞毒性,而又以CIL的細胞毒性最低,推測二聚體於細胞膜的吸附可能會因為其高電荷密度而提高細胞膜內外的電位差,但由於部分CIL可能會與膜上巰基蛋白形成雙硫鍵,並因為濃度梯度而轉移至膜內側,所以降低膜干擾的程度而提高生物相容性。因此CIL以可斷鍵形式所形成的二聚體提供一個理想基因沉默輸送的選擇。
摘要(英) Overexpression of tumor necrosis factor α (TNF-α) has been indicated as a key cytokine in many inflammatory diseases. In this study, we tended to inhibit TNF-α by gene therapy to promote its clinical application. Indolicidin (IL) is a potential cell-penetrating peptide (CPP); however, its application is restrict due to high cytotoxicity. In this study, we modified IL as dimers and investigated the effect of their cleavability on oligodeoxynucleotide (ODN) delivery efficiency. We added a cysteine residue to the N terminus of IL and denoted it as CIL. The HPLC and SDS-PAGE results demonstrated that this cysteine modification led CIL to self-crosslink as dimers through disulfide bond formation. In addition, we developed a dimeric peptide mimicking CIL and replaced its cysteine with serine, and denoted it as S28. Because both CIL and S28 own more positive charges and larger molecular weights, the results of DLS and gel retardation assay showed that these dimers effectively encapsulated ODN to form stable complexes compared to the IL group, and these particles were all suitable for macrophage uptake. Fluorescent labeling was applied to track ODN delivery, which suggested that both CIL and S28 not only promoted ODN internalization but also facilitated endosomal escape. To evaluate gene silence efficiency, these peptides were applied to RNAi experiments against TNF-α. The results demonstrated that TNF-α expression was highly inhibited by CIL and S28 compared to that of IL. Hemolytic activity and MTT assays were applied biocompatibility evaluation, which indicated that dimeric peptides demonstrated lower membrane perturbation and cytotoxicity that those of IL. Interesting, CIL was the one with the lowest cytotoxicity, We deduced that CIL may form disulfide bonds with exofacial thiols of cell membrance and migrate to the inner side of membrane due to a concentration gradient, so the degree of charge accumulation outside the membrane was not as serious as that of S28, which thus decreased membrane perturbation and increased biocompatibility. Therefore, CIL as a cleavable dimeric peptide provided an ideal choice for ODN delivery.
關鍵字(中) ★ 胜?
★ 二聚體
★ 半胱胺酸
★ 去氧寡核?酸
★ 基因輸送
關鍵字(英) ★ peptide
★ dimer
★ cysteine
★ oligodeoxynucleotide
★ gene delivery
論文目次 摘要 I
Abstract II
目錄 V
圖目錄 IX
表目錄 XI
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 4
2-1免疫反應 4
2-1-1免疫系統 4
2-1-2 免疫失調疾病 4
2-1-2-1腫瘤壞死因子(Tumor necrosis factor α) 5
2-1-2-2現有免疫疾病治療方式 5
2-2基因治療 7
2-2-1基因沉默 8
2-2-1-1核糖核酸干擾 9
2-2-1-2反義寡核?酸 11
2-3基因載體 13
2-3-1病毒型載體 13
2-3-2 非病毒型載體 13
2-3-2-1 脂質體 14
2-3-2-2 陽離子型高分子 14
2-4 胜? 15
2-4-1 細胞穿膜胜? 15
2-4-2 細胞穿膜胜?進入細胞的機制 17
2-4-3 Indolicidin 18
2-4-4 Indolicidin的穿膜機制 19
2-5 以二聚體形式應用於藥物輸送 20
第三章 材料與方法 24
3-1實驗材料 24
3-1-1合成材料 24
3-1-2細胞培養用藥 25
3-1-3定性定量分析試劑 25
3-2實驗儀器 27
3-3實驗方法 32
3-3-1溶液配置 32
3-3-2 HPLC分析 36
3-3-3 蛋白質膠體電泳(SDS-PAGE)分析 37
3-3-4 複合物(Peptide/ODN)製備 40
3-3-5 粒徑大小與表面電位(DLS) 41
3-3-6 包覆率 42
3-3-6-1製膠(1% agarose膠片) 42
3-3-6-2跑膠與照膠 42
3-3-6-3螢光標定法 43
3-3-7 胜?溶血活性 44
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) 46
3-3-8-4蛋白質抑制實驗 47
3-3-8-4-1 轉染 47
3-3-8-4-2 Lipopolysaccharide (LPS) Treatment 47
3-3-8-4-3 MTT assay for Normalization 48
3-3-8-4-4 ELISA分析 48
第四章 結果與討論 50
4-1二聚體分析 50
4-1-1 HPLC分析 50
4-1-2 SDS-PAGE分析 52
4-2奈米粒子物性鑑定 53
4-2-1 表面電位 53
4-2-2 粒徑大小 55
4-2-3 包覆率 56
4-3生物適合性測試 58
4-3-1溶血活性(人類紅血球細胞) 58
4-3-2 MTT分析 60
4-4複合物對細胞攝取的影響 62
4-4-1螢光顯微鏡分析細胞攝取量 62
4-4-2雷射共軛焦顯微鏡探討細胞攝取 64
4-4-3 複合物對蛋白質表現的影響 66
第五章 結論 68
第六章 參考文獻 70
參考文獻 1. Palladino, M.A., et al., Anti-TNF-alpha therapies: The next generation. Nature Reviews Drug Discovery, 2003. 2(9): p. 736-746.
2. Moss, M.L., L. Sklair-Tavron, and R. Nudelman, Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nature Clinical Practice Rheumatology, 2008. 4(6): p. 300-309.
3. Newton, R.C., et al., Biology of TACE inhibition. Annals of the Rheumatic Diseases, 2001. 60: p. III25-III32.
4. Gould, D.J., C. Bright, and Y. Chernajovsky, Inhibition of established collagen-induced arthritis with a tumour necrosis factor-alpha inhibitor expressed from a self-contained doxycycline regulated plasmid. Arthritis Research & Therapy, 2004. 6(2): p. R103-R113.
5. Petros, R.A. and J.M. DeSimone, Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery, 2010. 9(8): p. 615-627.
6. Ferber, D., Gene therapy: Safer and virus-free? Science, 2001. 294(5547): p. 1638-1642.
7. Fosgerau, K. and T. Hoffmann, Peptide therapeutics: current status and future directions. Drug Discovery Today, 2015. 20(1): p. 122-128.
8. Tsai, C.W., et al., The consideration of indolicidin modification to balance its hemocompatibility and delivery efficiency. International Journal of Pharmaceutics, 2015. 494(1): p. 498-505.
9. Hu, W.-W., et al., A novel application of indolicidin for gene delivery. International Journal of Pharmaceutics, 2013. 456(2): p. 293-300.
10. Tsai, C.W., et al., Coupling molecular dynamics simulations with experiments for the rational design of indolicidin-analogous antimicrobial peptides. J Mol Biol, 2009. 392(3): p. 837-54.
11. Hoyer, J., et al., Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery. Beilstein J Org Chem, 2012. 8: p. 1788-97.
12. Kim, H., M. Kitamatsu, and T. Ohtsuki, Enhanced intracellular peptide delivery by multivalent cell-penetrating peptide with bioreducible linkage. Bioorganic & Medicinal Chemistry Letters, 2018. 28(3): p. 378-381.
13. Amand, H.L., B. Norden, and K. Fant, Functionalization with C-terminal cysteine enhances transfection efficiency of cell-penetrating peptides through dimer formation. Biochem Biophys Res Commun, 2012. 418(3): p. 469-74.
14. Moser, M. and O. Leo, Key concepts in immunology. Vaccine, 2010. 28: p. C2-C13.
15. Medzhitov, R., Recognition of microorganisms and activation of the immune response. Nature, 2007. 449(7164): p. 819-26.
16. Carswell, E.A., et al., An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A, 1975. 72(9): p. 3666-70.
17. Van Deventer, S.J., Tumour necrosis factor and Crohn′s disease. Gut, 1997. 40(4): p. 443-8.
18. Matsuno, H., et al., The role of TNF-alpha in the pathogenesis of inflammation and joint destruction in rheumatoid arthritis (RA): a study using a human RA/SCID mouse chimera. Rheumatology, 2002. 41(3): p. 329-337.
19. Huang, Z., et al., The effect of targeted delivery of anti-TNF-alpha oligonucleotide into CD169+ macrophages on disease progression in lupus-prone MRL/lpr mice. Biomaterials, 2012. 33(30): p. 7605-12.
20. D.Health, Our inheritance, our future: realising the potential of genetics in the NHS. Genetics White Paper, 2003: p. chapter 1.25, 2003.
21. K. B. Kaufmann, H.B., A. Galy, A. Schambach, and M. Grez, "Gene therapy on the move, Gene therapy on the move. Embo Molecular Medicine, vol. 5, pp. 1642-1661, 2013.
22. K. Kaushansky, M.A.L., J.T. Prchal, M.M. Levi, O.W. Press, L.J. Burns, M., Williams Hematology, 9th edition. 2006.
23. Kurreck, J., Antisense technologies. Improvement through novel chemical modifications. Eur J Biochem, 2003. 270(8): p. 1628-44.
24. de Fougerolles, A., et al., Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov, 2007. 6(6): p. 443-53.
25. Grimm, D. and M.A. Kay, Therapeutic application of RNAi: is mRNA targeting finally ready for prime time? Journal of Clinical Investigation, 2007. 117(12): p. 3633-3641.
26. Elsabahy, M., A. Nazarali, and M. Foldvari, Non-Viral Nucleic Acid Delivery: Key Challenges and Future Directions. Current Drug Delivery, 2011. 8(3): p. 235-244.
27. Bartel, D.P., MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004. 116(2): p. 281-97.
28. Khatri, N., et al., In vivo delivery aspects of miRNA, shRNA and siRNA. Crit Rev Ther Drug Carrier Syst, 2012. 29(6): p. 487-527.
29. Rao, D.D., et al., siRNA vs. shRNA: similarities and differences. Adv Drug Deliv Rev, 2009. 61(9): p. 746-59.
30. Martinez, J., et al., Single-stranded antisense siRNAs guide target RNA cleavage in RNAi. Cell, 2002. 110(5): p. 563-74.
31. Whitehead, K.A., R. Langer, and D.G. Anderson, Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov, 2009. 8(2): p. 129-38.
32. Crooke, S.T., Progress in antisense technology. Annu Rev Med, 2004. 55: p. 61-95.
33. Dias, N. and C.A. Stein, Antisense oligonucleotides: basic concepts and mechanisms. Mol Cancer Ther, 2002. 1(5): p. 347-55.
34. Forte, A., et al., Small interfering RNAs and antisense oligonucleotides for treatment of neurological diseases. Curr Drug Targets, 2005. 6(1): p. 21-9.
35. Dinc, E., Antisense Oligodeoxynucleotide Technology: A Novel Tool for Gene Silencing in Higher Plants. Institute of Plant Biology Biological Research Centre Hungarian Academy of Sciences Doctoral School of Biology University of Szeged, 2012.
36. Emine, M.D., Antisense Oligodeoxynucleotide Technology:A Novel Tool for Gene Silencing in Higher Plants. 2012.
37. Jackson, A.L., et al., Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. Rna, 2006. 12(7): p. 1179-87.
38. Wang, J., et al., Delivery of siRNA therapeutics: barriers and carriers. Aaps j, 2010. 12(4): p. 492-503.
39. Paddison, P.J., et al., Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev, 2002. 16(8): p. 948-58.
40. Chen, Y., G. Cheng, and R.I. Mahato, RNAi for treating hepatitis B viral infection. Pharm Res, 2008. 25(1): p. 72-86.
41. Kariko, K., et al., Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through toll-like receptor 3. J Immunol, 2004. 172(11): p. 6545-9.
42. Crystal, R.G., Transfer of genes to humans: early lessons and obstacles to success. Science, 1995. 270(5235): p. 404-10.
43. Al-Dosari, M.S. and X. Gao, Nonviral gene delivery: principle, limitations, and recent progress. Aaps j, 2009. 11(4): p. 671-81.
44. Santos, J.L., et al., Non-viral gene delivery to mesenchymal stem cells: methods, strategies and application in bone tissue engineering and regeneration. Curr Gene Ther, 2011. 11(1): p. 46-57.
45. Impellizeri, J., et al., Electroporation in veterinary oncology. Veterinary Journal, 2016. 217: p. 18-25.
46. Titomirov, A.V., S. Sukharev, and E. Kistanova, In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim Biophys Acta, 1991. 1088(1): p. 131-4.
47. Mir, L.M., Electroporation-based gene therapy: recent evolution in the mechanism description and technology developments. Methods Mol Biol, 2014. 1121: p. 3-23.
48. Yang, N.S., et al., In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad Sci U S A, 1990. 87(24): p. 9568-72.
49. Uchida, M., et al., 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, 2002. 25(5): p. 690-693.
50. Poste, G., D. Papahadjopoulos, and W.J. Vail, Lipid vesicles as carriers for introducing biologically active materials into cells. Methods Cell Biol, 1976. 14: p. 33-71.
51. Chen, C.T., et al., Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB. Acs Applied Materials & Interfaces, 2017. 9(7): p. 5864-5873.
52. Gaber, M., et al., Protein-lipid nanohybrids as emerging platforms for drug and gene delivery: Challenges and outcomes. Journal of Controlled Release, 2017. 254: p. 75-91.
53. Hellstrand, E., et al., Membrane lipid co-aggregation with alpha-synuclein fibrils. PLoS One, 2013. 8(10): p. e77235.
54. Akhtar, S., et al., The delivery of antisense therapeutics. Adv Drug Deliv Rev, 2000. 44(1): p. 3-21.
55. Lebedeva, I., et al., Cellular delivery of antisense oligonucleotides. Eur J Pharm Biopharm, 2000. 50(1): p. 101-19.
56. Zelphati, O., et al., Effect of serum components on the physico-chemical properties of cationic lipid/oligonucleotide complexes and on their interactions with cells. Biochimica Et Biophysica Acta-Lipids and Lipid Metabolism, 1998. 1390(2): p. 119-133.
57. Ulasov, A.V., et al., Properties of PEI-based polyplex nanoparticles that correlate with their transfection efficacy. Mol Ther, 2011. 19(1): p. 103-12.
58. Grzelinski, M., et al., RNA interference-mediated gene silencing of pleiotrophin through polyethylenimine-complexed small interfering RNAs in vivo exerts antitumoral effects in glioblastoma xenografts. Hum Gene Ther, 2006. 17(7): p. 751-66.
59. Ewe, A., et al., Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model. Drug Deliv Transl Res, 2017. 7(2): p. 206-216.
60. Bellich, B., et al., "The Good, the Bad and the Ugly" of Chitosans. Marine Drugs, 2016. 14(5): p. 31.
61. Frankel, A.D. and C.O. Pabo, Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 1988. 55(6): p. 1189-93.
62. Green, M. and P.M. Loewenstein, Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell, 1988. 55(6): p. 1179-88.
63. Joliot, A., et al., Antennapedia homeobox peptide regulates neural morphogenesis. Proc Natl Acad Sci U S A, 1991. 88(5): p. 1864-8.
64. Guidotti, G., L. Brambilla, and D. Rossi, Cell-Penetrating Peptides: From Basic Research to Clinics. Trends Pharmacol Sci, 2017. 38(4): p. 406-424.
65. Regberg, J., A. Srimanee, and U. Langel, Applications of cell-penetrating peptides for tumor targeting and future cancer therapies. Pharmaceuticals (Basel), 2012. 5(9): p. 991-1007.
66. Hoyer, J. and I. Neundorf, Peptide vectors for the nonviral delivery of nucleic acids. Acc Chem Res, 2012. 45(7): p. 1048-56.
67. Wagner, E., M. Ogris, and W. Zauner, Polylysine-based transfection systems utilizing receptor-mediated delivery. Adv Drug Deliv Rev, 1998. 30(1-3): p. 97-113.
68. Rothbard, J.B., et al., Arginine-rich molecular transporters for drug delivery: role of backbone spacing in cellular uptake. J Med Chem, 2002. 45(17): p. 3612-8.
69. Trabulo, S., et al., Cell-Penetrating Peptides—Mechanisms of Cellular Uptake and Generation of Delivery Systems. Pharmaceuticals, 2010. 3(4): p. 961.
70. Khalil, I.A., et al., High density of octaarginine stimulates macropinocytosis leading to efficient intracellular trafficking for gene expression. Journal of Biological Chemistry, 2006. 281(6): p. 3544-3551.
71. Kaplan, I.M., J.S. Wadia, and S.F. Dowdy, Cationic TAT peptide transduction domain enters cells by macropinocytosis (vol 102, pg 247, 2005). Journal of Controlled Release, 2005. 107(3): p. 571-572.
72. Poon, G.M.K. and J. Gariepy, Cell-surface proteoglycans as molecular portals for cationic peptide and polymer entry into cells. Biochemical Society Transactions, 2007. 35: p. 788-793.
73. Nakase, I., et al., Interaction of arginine-rich peptides with membrane-associated proteoglycans is crucial for induction of actin organization and macropinocytosis. Biochemistry, 2007. 46(2): p. 492-501.
74. Mishra, A., et al., Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions. Proceedings of the National Academy of Sciences of the United States of America, 2011. 108(41): p. 16883-16888.
75. Selsted, M.E., et al., Indolicidin, a novel bactericidal tridecapeptide amide from neutrophils. J Biol Chem, 1992. 267(7): p. 4292-5.
76. Bechinger, B., M. Zasloff, and S.J. Opella, Structure and orientation of the antibiotic peptide magainin in membranes by solid-state nuclear magnetic resonance spectroscopy. Protein Sci, 1993. 2(12): p. 2077-84.
77. Zhang, L., A. Rozek, and R.E. Hancock, Interaction of cationic antimicrobial peptides with model membranes. J Biol Chem, 2001. 276(38): p. 35714-22.
78. Erazo-Oliveras, A., et al., Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges. Pharmaceuticals (Basel), 2012. 5(11): p. 1177-209.
79. Angeles-Boza, A.M., et al., Generation of endosomolytic reagents by branching of cell-penetrating peptides: tools for the delivery of bioactive compounds to live cells in cis or trans. Bioconjug Chem, 2010. 21(12): p. 2164-7.
80. Chugh, A., E. Amundsen, and F. Eudes, Translocation of cell-penetrating peptides and delivery of their cargoes in triticale microspores. Plant Cell Rep, 2009. 28(5): p. 801-10.
81. Sung, M., G.M. Poon, and J. Gariepy, The importance of valency in enhancing the import and cell routing potential of protein transduction domain-containing molecules. Biochim Biophys Acta, 2006. 1758(3): p. 355-63.
82. Tung, C.H., S. Mueller, and R. Weissleder, Novel branching membrane translocational peptide as gene delivery vector. Bioorg Med Chem, 2002. 10(11): p. 3609-14.
83. Rudolph, C., et al., Oligomers of the arginine-rich motif of the HIV-1 TAT protein are capable of transferring plasmid DNA into cells. J Biol Chem, 2003. 278(13): p. 11411-8.
84. McKenzie, D.L., K.Y. Kwok, and K.G. Rice, A potent new class of reductively activated peptide gene delivery agents. J Biol Chem, 2000. 275(14): p. 9970-7.
85. Moon, I.J., et al., Marked transfection enhancement by the DPL (DNA/peptide/lipid) complex. Int J Mol Med, 2007. 20(4): p. 429-37.
86. Torres, A.G. and M.J. Gait, Exploiting cell surface thiols to enhance cellular uptake. Trends Biotechnol, 2012. 30(4): p. 185-90.
87. Rudolph, C., et al., Application of novel solid lipid nanoparticle (SLN)-gene vector formulations based on a dimeric HIV-1 TAT-peptide in vitro and in vivo. Pharm Res, 2004. 21(9): p. 1662-9.
88. Lee, S.J., S.H. Yoon, and K.O. Doh, Enhancement of gene delivery using novel homodimeric tat peptide formed by disulfide bond. J Microbiol Biotechnol, 2011. 21(8): p. 802-7.
89. Kim, B.K., et al., Homodimeric SV40 NLS peptide formed by disulfide bond as enhancer for gene delivery. Bioorg Med Chem Lett, 2012. 22(17): p. 5415-8.
90. Green, T.R., et al., Polyethylene particles of a ′critical size′ are necessary for the induction of cytokines by macrophages in vitro. Biomaterials, 1998. 19(24): p. 2297-302.
91. Tsai, C.W., et al., Development of an indolicidin-derived peptide by reducing membrane perturbation to decrease cytotoxicity and maintain gene delivery ability. Colloids and Surfaces B-Biointerfaces, 2018. 165: p. 18-27.
92. Gasparini, G., et al., Cellular Uptake of Substrate-Initiated Cell-Penetrating Poly(disulfide)s. Journal of the American Chemical Society, 2014. 136(16): p. 6069-6074.
93. Liu, Y., et al., Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem, 1997. 69(2): p. 581-93.
94. Dong, L., et al., Targeting delivery oligonucleotide into macrophages by cationic polysaccharide from Bletilla striata successfully inhibited the expression of TNF-alpha. J Control Release, 2009. 134(3): p. 214-20.
指導教授 胡威文(Wei-Wen Hu) 審核日期 2018-8-23
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