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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 化學工程學系
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23173
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dc.contributor.advisor彭慶安(Ching-An Peng)
dc.contributor.authorChia-Wei Changen
dc.contributor.author張家瑋zh_TW
dc.date.accessioned2021-06-08T04:45:42Z-
dc.date.copyright2009-08-05
dc.date.issued2009
dc.date.submitted2009-07-31
dc.identifier.citation1. A. M. Iga, J. H.P. Robertson, M.C. Winslet, A.M. Seifalian. Clinical potential of quantum dots. Journal of Biomedicine and Biotechnology (2007) doi:10.1155/2007/76087.
2. S. C. McBain, H. H.P. Yiu, J. Dobson. Magnetic nanoparticles for gene and drug delivery. International Journal of Nanomedicine 3 (2008) 169-180.
3. X. Huang, P. K. Jain, I. H. El-Sayed, M. A. El-Sayed. Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostic and therapy. Nanomedicine 2 (2007) 681-693.
4. N. J. Durr, T. Larson, D. K. Smith, et al. Two-photon luminescence imaging of cancer cells using molecularly targeted gold nanorods. Nano Letters 7 (2007) 941-945.
5. A. K. Oyelere, P. C. Chen, X. Huang, et al. Peptide-conjugated gold nanorods for nuclear targeting. Bioconjugate Chemistry 18 (2007) 1490-1497.
6. C. C. Chen, Y. P. Lin, C. W. Wang, et al. DNA-gold nanorods conjugates for remote control of localized gene expression by near infrared irradiation. Journal of American Chemical Society 128 (2006) 3709-3715.
7. C. A. Foss Jr, G. L. Hornyak, J. A. Stockert, C. R. Martin. Template-synthesized nanoscopic gold nanorods: optical spectra and the effects of particle size and shape. Journal of Physical Chemistry 98 (1994) 2963-2971.
8. J. Gao, C. M. Bender, C. J. Murphy. Dependence of the gold nanorod aspect ratio on the nature of the directing surfactant in aqueous solution. Langmuir 19 (2003) 9065-9070.
9. N. R. Jana, L. Gearheart, C. J. Murphy. Wet chemical synthesis of high aspect ratio cylindrical gold nanorods. Journal of Physical Chemistry B 105 (2001) 4065-4067.
10. B. Nikoobakht, M. A. El-Sayed. Evidence for bilayer assembly of cationic surfactants on the surface of gold nanorods. Langmuir 17 (2001) 6368-6374.
11. S. Link, M. B. Mohamed, M. A. El-Sayed. Stimulation of the optical absorption spactra of gold nanorods as a function of their aspect ratio and the effect of the medium dielectric constant. Journal of Physical Chemistry B 103 (1999) 3073-3077.
12. C. J. Orendorff, C. J. Murphy. Quantitation of metal content in the silver-assisted growth of gold nanorods. Journal of Physical Chemistry B 110 (2006) 3990-3994.
13. L. Tong, Q. Wei, A. Wei, J. X. Cheng. Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects. Photochemistry and photobiology 85 (2009) 21-32.
14. T. K. Sau, C. J. Murphy. Seeded high yield synthesis of short Au nanorods in aqueous solution. Langmuir 20 (2004) 6414-6420.
15. E. E. Connor, J. Mwamuka, A. Cole, et al. Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1 (2005) 325-327.
16. A. M. Alkilany, P. K. Nagaria, C. R. Hexel, et al. Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects. Small 5 (2009) 701-708.
17. H. Liao, L. H. Hafner. Gold nanorods bioconjugates. Chemistry of Materials 17 (2005) 4636-4641.
18. T. Niidome, M. Yamagata, Y. Okamoto, et al. PEG-modified gold nanorods with a stealth character for in vivo application. Journal of Controlled Release 114 (2006) 343-347.
19. T. B. Huff, M. N. Hansen, Y. Zhao, et al. Controlling the cellular uptake of gold nanorods. Langmuir 23 (2007) 1596-1599.
20. T. S. Hauck, A. A. Ghazani, W. C.W. Chan. Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. Small 4 (2008) 153-159.
21. Q. Dai, J. Coutts, J. Zou, Q. Huo. Surface modification of gold nanorods through a place exchange reaction inside an ionic exchange resin. Chemical communications 25 (2008) 2858-2860.
22. O. Felt, P. Buri, R. Gurny. Chitosan: a unique polysaccharide for drug delivery. Drug Development and Industrial Pharmacy 24 (1998) 979-993.
23. T. H. Kim, H. L. Jiang, D. Jere, et al. Chemical modification of chitosan as a gene carrier in vitro and in vivo. Progress in Polymer Science 32 (2007) 726-753.
24. J. H. Cho, S. H. Kim, K. D. Park, et al. Chondrogenic differentiation of human mesenchymal stem cells using a thermosensitive poly(N-isopropylacrylamide) and water-soluble chitosan copolymer. Biomaterials 25 (2004) 5743-5751.
25. X. F. Liu, Y. L. Guan, D. Z. Yang, et al. Antibacterial action of chitosan carboxymethylated chitosan. Journal of Applied Polymer Science 79 (2001) 1324-1335.
26. M. D. Cathell, J. C. Szewczyk, F. A. Bui, et al. Structurally colored thiol chitosan thin films as a platform for aqueous heavy metal ion detection. Biomacromolecules 9 (2008) 289-295.
27. S. R. Bhattarai, R. B. Kc, S. Y. Kim, et al. N-hexanoyl chitosan stabilized magnetic nanoparticles: Implication for cellular labeling and magnetic resonance imaging. Journal of Nanobiotechnology (2008) doi:10.1186/1477-3155-6-1
28. J. M. Maris, K. K. Matthay. Molecular biology of neuroblastoma. Journal of Clinical Oncology 17 (1999) 2264-2279.
29. B. De Bernardi, B. Nicolas, L. Boni, et al. Disseminated neuroblastoma in children older than one year at diagnosis: comparable results with three consecutive high-dose protocols adopted by the Italian Co-Operative Group for Neuroblastoma. Journal of Clinical Oncology 21 (2003) 1592–1601.
30. S. Hakomori. Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines. Advances in experimental medicine and biology 491 (2001) 369-402.
31. C. P. Reynolds, K. K. Matthay, J. G. Villablanca, et al. Retinoid therapy of high-risk neuroblastoma. Cancer Letters 197 (2003) 185-192.
32. L. Raffaghello, D. Marimpietri, G. Pagnan, et al. Anti-GD2 monoclonal antibody immunotherapy: a promising strategy in the development of neuroblastoma relapse. Cancer Letters 197 (2003)205-209.
33. C. Brignole, F. Pastorino, D. Marimpietri, et al. Immune cell-mediated antitumor activities of GD2 targeted liposomal c-myb antisense oligonucleotides containing CpG motifs. Journal of the National Cancer Institute 96 (2004) 1171-1180.
34. N. K. Cheung, U. M. Saarinen, J. E. Neely, et al. Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Research 45 (1985) 2642-2649.
35. G. Schulz, D. A. Cheresh, N. M. Varki, et al. Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients. Cancer Research 44 (1984) 5914-5920.
36. C. Nieder, M. P. Mehta, R. Jalali. Combined radio- and chemotherapy of brain tumors in adult patients. Clinical Oncology (2009), doi:10.1016/j.clon.2009.05.003
37. M. E. Hegi, A. C. Diserens, T. Gorlia. et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine 352 (2005) 997-1003.
38. R. Stupp, W. P. Mason, M. J. van den Bent, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New England Journal of Medicine 352 (2005) 987-996.
39. Y. Yu, A. Flint, E. L. Dvorin, J. Bischoff. AC133-2, a novel isoform of human AC133 stem cell antigen. Journal of Biological Chemistry 277 (2002) 20711-20716.
40. S. Miraglia, W. Godfrey, A. H. Yin, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood 90 (1997) 5013-5021.
41. S. K. Singh, I. D. Clarke, M. Terasaki, et al. Identification of a cancer stem cell in human brain tumors. Cancer Research 63 (2003) 5821-5828.
42. S. Bao, Q. Wu, R. E. McLendon, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444 (2006) 756-760.
43. N. Y. Frank, A. Margaryan, Y. Huang, et al. ABCB5-mediated doxorubicin transport and chemoresistance in human malignant melanoma. Cancer Research 65 (2005) 4320-4333.
44. N. W.S. Kam, M. O’Connell, J. A. Wisdom, and H. Dai. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc Natl Acad Sci U S A 102 (2005) 11600-11605.
45. P. Chakravarty, R. Marches, N. S. Zimmerman, et al. Thermal ablation of tumor cells with antibody-functionalized single-walled carbon nanotubes. Proc Natl Acad Sci U S A 105 (2008) 8697-8702.
46. L. R. Hirsch, R. J. Stafford, J. A. Bankson, et al. Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci U S A 100 (2003) 13549-13554.
47. D. P. O’Neal, L. R. Hirsch, N. J. Halas, et al. Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Letters 209 (2004) 171-176.
48. J. Chen, D. Wang, J. Xi, et al. Immuno gold nanocages with tailored optical properties for targeted photothermal destruction of cancer cells. Nano Letters 7 (2007) 1318-1322.
49. L. Tong, Y. Zhao, T. B. Huff, et al. Gold nanorods mediate tumor cell death by compromising membrane integrity. Advanced Materials 19 (2007) 3136-3141.
50. K. L.B. Chang, M. C. Tai, F. H. Cheng. Kinetics and products of the degradation of chitosan by hydrogen peroxide. Journal of Agricultural and Food Chemistry 49 (2001) 4845-4851.
51. M. D. Hornof, C. E. Kast, A. Bernkop-Schnürch. In vitro evaluation of the viscoelastic properties of chitosan-thioglycolic acid conjugates. European Journal of Pharmaceutics and Biopharmaceutics 55 (2003) 185-190
52. B. Nikoobaht, M. A. El-Sayed. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chemistry of Materials 15 (2003) 1957-1962.
53. M. Büttner, T. Belser, P. Oelhafen. Stability of thiol-passivated gold particles as elevated temperatures studied by X-ray photoelectron spectroscopy. Journal of Physical Chemistry B 109 (2005) 5464-5467.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23173-
dc.description.abstract奈米金柱在癌症治療領域上展現出無窮的潛力。因為奈米金柱經由精準的控制長寬比,可吸收位於生物光學窗範疇之近紅外光,進而轉變成熱能,故能在光熱治療中使用。製作奈米金柱的過程中,大多使用溴化十六烷三甲基銨(CTAB)做為介面活性劑。由於CTAB的生物不相容性,所以使用CTAB來製備奈米金柱,必須對奈米金柱的表面進行改質,以利應用於細胞相關之研究。生物相容性極高的甲殼素接上硫基後與奈米金柱混合,硫基會在奈米金柱的表面產生Au-S鍵結。因此,藉由ligand exchange程序可使硫基化的甲殼素將CTAB自原始的奈米金柱表面置換出來,以提昇生物相容性。甲殼素在接枝硫基後剩餘之胺基,可用來進一步與抗體鍵結。本論文中,將兩種單株抗體,anti-GD2以及anti-CD133,分別與奈米金柱鍵結;接著將標記上單株抗體之奈米金柱分別置入含有神經母細胞瘤(neuroblastoma cells)及 神經膠母細胞瘤 (glioblastoma cells)的培養皿內,觀察腫瘤細胞以胞飲作用將標記上單株抗體之奈米金柱噬入之情形。接著使用808 奈米波長的二極體雷射系統,令奈米金柱吸收近紅外光波段的光,進而轉變成可摧毀腫瘤細胞之熱能。zh_TW
dc.description.abstractGold nanorod (GNR) has great potential in cancer therapy field, because of its unique photophysical property in converting near-infrared (NIR) laser light into heat. GNRs fabricated by seed-mediated growth method with the aid of surfactant hexadecyltrimethylammonium bromide (CTAB) have been widely used. However, due to strong cytotoxicity of CTAB, it is necessary to modify the surface of GNRs for cell-related studies. In this study, thiolated chitosan was synthesized and harnessed to replace CTAB originally used for stabilizing gold nanorods. The degree of thiol groups immobilized on chitosan was quantitatively determined by Ellman’s analysis. The average size of GNR and thiolated chitosan-modified GNR (CGNR) determined by dynamic light scattering (DLS) was 66 nm and 84.9 nm, respectively which are consistent with the images obtained by transmission electron microscopy (TEM). X-ray photoelectron spectroscopy (XPS) was used to confirm the existence of Au-S binding energy at 162.4 eV. Cytotoxicity study revealed that CGNR was much biocompatible than CTAB-stabilized GNR.
CGNRs were further conjugated with two different kinds of monoclonal antibodies: anti-GD2 and anti-CD133. The former antibody can specifically target neuroblastoma cells and the latter one is able to recognize glioblastoma stem-like cells. Our results showed that CGNRs functionalized with specific monoclonal antibody could be internalized by its corresponding cancer cells via receptor-mediated endocytosis. NIR laser was then used to irradiate CGNR-laden cells for pre-determined power intensity and exposure time. The viability of NIR laser treated cells examined by calcein-AM dye demonstrated that cancer cells ingested with antibody-tagged CGNRs and irradiated with 808-nm NIR laser light were all found to undergo necrosis.
en
dc.description.provenanceMade available in DSpace on 2021-06-08T04:45:42Z (GMT). No. of bitstreams: 1
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Previous issue date: 2009
en
dc.description.tableofcontents口試委員會審定書..............................i
致謝.........................................ii
中文摘要....................................iii
Abstract.....................................iv
Contents.....................................vi
Introduction..................................1
Experimental section.........................10
Materials....................................10
Instruments..................................13
Methods......................................14
Characterization.............................17
Results and Discussion.......................23
Conclusions..................................29
Suggested Future Work........................30
References...................................32
Scheme I. Reaction scheme of thiolated chitosan...40
Scheme II. Reaction scheme of CTAB-stabilized gold nanorods..........................................41
Scheme III. Reaction scheme of thiolated chitosan-modified gold nanorod......................................42
Table I. Amount of reagents used for synthesis of thiolated chitosan and the content of thiol moieties immobilized on different molecular weights of chitosan...........43
Figure 1. Absorption spectra of CTAB-stabilized gold nanorods (solid line) and thiolated chitosan-modified gold nanorods (dash line)..............................44
Figure 2. Size distribution of (a) GNR and (b) CGNR determined by dynamic light scattering............45
Figure 3. TEM images of (a) GNR with aspect ratio of 3.84 ± 0.64 and (b) CGNR with a grey shell around GNR....46
Figure 4. The S2p spectra of (a) GNR and (b) CGNR. The Au4f spectra of (c) GNR and (d) CGNR...................47
Figure 5. Effect of GNR and CGNR on the morphology and growth of NIH 3T3 cells. (I) control group, (II) cells challenged with GNRs, (III) cells challenged with CGNRs (scale bar = 50 μm)..............................48
Figure 6. Cell viability of NIH 3T3 cells treated separately with different concentrations of GNRs and CGNRs and determined by MTT assay. Data shown here were the mean ±SD of triplicate experiments......................49
Figure 7. Confocal images of stNB-V1 (GD2+ cells) and NIH 3T3 (GD2- cells) cultured with rhodamine B labeled anti-GD2-CGNR for 6 hr, respectively (scale bar = 10 μm)..50
Figure 8. Temperature rising curves of different concentrations of CGNRs suspended in PBS solution and irradiated with 808-nm NIR laser light............51
Figure 9. Photothermal treatment of stNB-V1 (GD2+ cells) and NIH 3T3 (GD2- cells) after exposed with 808-nm NIR laser light and stained with calcein-AM dye afterwards (scale bar = 100 μm)..............................52
Figure 10. Confocal images of GBM S1R1 (CD133+ cells) and MED DAOY (CD133- cells) cultured with anti-CD133-CGNR for 6 hr, respectively (black scale bar = 10 μm and white scale bar = 25 μm)......................................53
Figure 11. Photothermal treatment of GBM S1R1 (CD133+ cells) and MED DAOY (CD133- cells) after exposed to 808-nm NIR laser light and stained with calcein-AM dye afterwards (scale bar = 100 μm)..............................54
Figure 12. Flow cytometric histogram of GBM S1R1 (CD133+ cells) and MED DAOY (CD133- cells) mixed with different ratios (3:1, 1:1, and 1:3). Mixed cells were co-cultured with anti-CD133-CGNR for 6 h, beamed with 808-nm NIR laser, stained with calcein-AM, and then analyzed by a flow cytometer..........................................55
dc.language.isoen
dc.subject光熱療法zh_TW
dc.subject奈米金柱zh_TW
dc.subject單株抗體CD133zh_TW
dc.subject單株抗體GD2zh_TW
dc.subjectgold nanoroden
dc.subjectanti-GD2en
dc.subjectphotothermal therapyen
dc.subjectanti-CD133en
dc.title奈米金柱鍵結上單株抗體對腫瘤細胞進行光熱療法zh_TW
dc.titlePhotothermolysis of Tumor Cells Using Gold Nanorods Functionalized with Monoclonal Antibodyen
dc.typeThesis
dc.date.schoolyear97-2
dc.description.degree碩士
dc.contributor.oralexamcommittee徐文平,王鍾毅,林瑞騰
dc.subject.keyword奈米金柱,光熱療法,單株抗體GD2,單株抗體CD133,zh_TW
dc.subject.keywordgold nanorod,photothermal therapy,anti-GD2,anti-CD133,en
dc.relation.page55
dc.rights.note未授權
dc.date.accepted2009-07-31
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept化學工程學研究所zh_TW
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