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研究生: 賴宥儒
You-Ru Lai
論文名稱: 新型奈米金粒子之細胞攝入與表面拉曼光譜分析
A Novel Gold Nanoparticle of Cellular Uptake and Analysis for the Application of SERS
指導教授: 何明樺
Ming-Hua Ho
口試委員: 高震宇
Jhen-Yu Kao
李忠興
Chung-Sing Li
學位類別: 碩士
Master
系所名稱: 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年: 2016
畢業學年度: 104
語文別: 中文
論文頁數: 153
中文關鍵詞: 奈米金細胞攝入葉酸表面拉曼光譜
外文關鍵詞: gold nanoparticles, cellular uptake, folic acid, surface enhanced Raman scattering (SERS)
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本研究使用葉酸做為還原劑及保護劑,藉此合成出葉酸-奈米金,由穿透式電子顯微鏡結果顯示,葉酸-奈米金粒徑為17±6nm,隨儲存時間越久奈米粒子呈現越高的介達電位,當儲存7天後,葉酸-奈米金粒徑介於45到50nm間,並具有良好的穩定性。
細胞攝入實驗中,我們觀察了骨癌細胞(UMR)與骨母細胞(7F2)對葉酸-奈米金的攝入情形,當在高濃度奈米金的情況下,進入細胞的金粒子數量變多、且奈米金進入細胞核數量也隨之變多。由於骨癌細胞有葉酸受體表現,導致骨癌細胞攝入及胞吐奈米金速度相較於骨母細胞都較快,此外,奈米粒子在骨母細胞中滯留數量較多滯留時間也較久。
體外細胞實驗結果指出,在培養一段時間後,在高濃度葉酸-奈米金會抑制細胞活性與蛋白質分泌,這應該是因為較多粒子進入細胞核中、且粒子在細胞中滯留。此外,只要濃度低於30μM時葉酸-奈米金對於後期骨細胞的礦化即不會產生影響。
表面拉曼光譜結果顯示,葉酸-奈米金對細胞的拉曼訊號有增強的效應,特別是骨分化蛋白與amide III的訊號強度更是被大幅的提升,此外,葉酸-奈米金對骨癌細胞中得拉曼訊號表現出較佳的增強效果,這是因為癌細胞對葉酸-奈米金具有更高的攝入效率。


In this research, synthesis the folic acid conjugated gold nanoparticle (FA-GNP) in a simple way by taking folic acid as reducing agent and protecting agent. According to the results of transmission electron microscopy (TEM), the particle size is 17 ± 6 nm. The zeta potential of the FA-GNP increases with the storage time. After the immersion in aqueous solution for 7 days, the particle size of FA-GNP is up to 45 to 50 nm with good stability.
UMR (Rat osteogenic sarcoma) and 7F2 (Osteoblast) are used for cellular uptake of FA-GNP. When the concentration of FA-GNP is high and more FA-GNP were uptake and more FA-GNP enter the nucleus. UMR cells uptake more FA-GNP than 7F2 due to the folate receptor expression of UMR. Besides, the FA-GNP shows longer retention time in UMR.
According to in vitro tests, the FA-GNP doesn’t affect the viability and phenotypes of cells at the early stage of culture. With concentrated FA-GNP, more FA-GNP enter into cells and inhibit the cell viability and production of extracellular matrix. Furthermore, as the concentration of FA-GNP were lower than 30μM, FA-GNP shows no effect on the late stage of osteogenic differemtiation.
The results from surface enhanced Raman spectroscopy (SERS) indicate that the FA-GNP would be able to enhance the intensity of the Raman spectra The FA-GNP was especially effective on the SERS peaks for amide Ⅲ bondings, the characteristic functional groups in osteogenic differentiation. More important, the Raman signals of osteosarcoma are enhanced more than osteoblasts, which is caused by the targeting effect of FA-GNP.

摘要 I Abstract III 致謝 V 目錄 VII 圖目錄 XII 表目錄 XVIII 方程式目錄 XIX 專有名詞及縮寫 XX 第一章 緒論 1 第二章 文獻回顧 3 2.1 奈米科技 3 2.1.1 奈米科技的簡介 3 2.1.2 奈米材料的基本定義 3 2.2 奈米金粒子的特性、應用及製備 5 2.2.1 奈米金粒子的特性 5 2.2.2 奈米金粒子的製備 6 2.3 葉酸介紹 8 2.4 奈米金粒子與細胞之作用 10 2.4.1 奈米金粒子與細胞間的作用 10 2.4.2 奈米金尺寸對細胞毒性的影響 13 2.4.3 奈米金形狀對細胞毒性的影響 15 2.4.4 奈米金電性對細胞毒性的影響 16 2.4.5 奈米金表面改質對細胞毒性之影響 18 2.4.6 奈米金在生物醫學領域之應用 21 2.5 骨母細胞 23 2.5.1 骨母細胞來源 23 2.5.2 骨母細胞的分化標記 24 2.6 拉曼散射 27 2.6.1 拉曼散射之原理 27 2.6.2 拉曼散射之應用 32 2.6.3 表面增強拉曼散射之原理 33 2.6.4 表面增強拉曼散射之應用 34 2.7 實驗設計與目的 35 第三章 實驗材料與方法 36 3.1 實驗藥品 36 3.2 實驗儀器 38 3.3 實驗葉酸-奈米金粒子製備 40 3.3.1 葉酸奈米金粒子合成 40 3.3.2 葉酸-奈米金粒子物性分析 40 3.3.3 奈米金粒子之殺菌程序 40 3.4 體外細胞實驗 41 3.4.1 實驗操作 41 3.4.2 細胞來源 41 3.4.3 細胞培養 44 3.4.4 細胞冷凍保存 44 3.4.5 細胞解凍及培養 45 3.4.6 細胞計數 45 3.4.7 粒線體活性測試 48 3.4.8 鹼性磷酸酶測試 50 3.4.9 蛋白質濃度測定 52 3.4.10 Von Kossa染色 53 3.4.11 穿透式電子顯微鏡樣品製備 55 3.4.12 拉曼光譜檢測 57 第四章 結果與討論 58 4.1 奈米金粒子的物性分析 58 4.1.1 奈米金粒子型態分析及前處理 58 4.1.2 光譜分析 62 4.2 葉酸-奈米金粒子被細胞攝入的情形 65 4.2.1 不同時間下葉酸-奈米金粒子被細胞攝入的情形 65 4.2.2 相同細胞攝入時間比較不同濃度葉酸-奈米金粒子被細胞攝入的情形 79 4.3 奈米金粒子對細胞活性與表現型的影響 84 4.3.1 細胞粒線體活性測試 84 4.3.2 細胞總蛋白質 89 4.3.3 鹼性磷酸酶表現 92 4.3.4 細胞礦化(Von Kossa stain)與元素分析 96 4.3.5 表面增強拉曼散射檢測 103 第五章 結論 108 參考文獻 110

1. Chen, H.M., R.S. Liu, and D.P. Tsai, A Versatile Route to the Controlled Synthesis of Gold Nanostructures. Crystal Growth & Design, 2009. 9(5): p. 2079-2087.
2. Rosenstiel, S.F., M.F. Land, and B.J. Crispin, Dental luting agents: A review of the current literature. The Journal of Prosthetic Dentistry, 1998. 80(3): p. 280-301.
3. Gillibert, R., M. Sarkar, J.F. Bryche, R. Yasukuni, J. Moreau, G. Barbillon, B. Bartenlian, M. Canva, and M.L. Chapelle, Directional surface enhanced Raman scattering on gold nano-gratings. Nanotechnology, 2016. 27(11): p. 1-8.
4. Daniel, M.C. and D. Astruc, Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev, 2004. 104(1): p. 293-346.
5. Alivisatos, P., The use of nanocrystals in biological detection. Nat Biotech, 2004. 22(1): p. 47-52.
6. Brewer, S.H., W.R. Glomm, M.C. Johnson, M.K. Knag, and S. Franzen, Probing BSA Binding to Citrate-Coated Gold Nanoparticles and Surfaces. Langmuir, 2005. 21(20): p. 9303-9307.
7. Lacerda, S.H.D.P., J.J. Park, C. Meuse, D. Pristinski, M.L. Becker, A. Karim, and J.F. Douglas, Interaction of Gold Nanoparticles with Common Human Blood Proteins. ACS Nano, 2010. 4(1): p. 365-379.
8. Maxwell, D.J., J.R. Taylor, and S. Nie, Self-Assembled Nanoparticle Probes for Recognition and Detection of Biomolecules. Journal of the American Chemical Society, 2002. 124(32): p. 9606-9612.
9. Turkevich, J., G. Garton, and P.C. Stevenson, The color of colloidal gold. Journal of Colloid Science, 1954. 9: p. 26-35.
10. Frens, G., Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nature Physical Science, 1973. 241(105): p. 20-22.
11. Jana, N.R., L. Gearheart, and C.J. Murphy, Seed-Mediated Growth Approach for Shape-Controlled Synthesis of Spheroidal and Rod-like Gold Nanoparticles Using a Surfactant Template. Advanced Materials, 2001. 13(18): p. 1389-1393.
12. Jana, N.R.L.G., S.O. Obare, and C.J. Murphy, Anisotropic Chemical Reactivity of Gold Spheroids and Nanorods. Langmuir, 2002. 18(3): p. 922-927.
13. Jana, N.R., L. Gearheart, and C.J. Murphy, Wet Chemical Synthesis of High Aspect Ratio Cylindrical Gold Nanorods. The Journal of Physical Chemistry B, 2001. 105(19): p. 4065-4067.
14. Brust, M., M. Walker, D. Bethell, D.J. Schiffrin, and R. Whyman, Synthesis of thiol-derivatised gold nanoparticles in a two-phase Liquid?Liquid system. Journal of the Chemical Society, Chemical Communications, 1994(7): p. 801-802.
15. Aslam, M., L. Fu, M. Su, K. Vijayamohanan, and V.P. Dravid, Novel one-step synthesis of amine-stabilized aqueous colloidal gold nanoparticles. Journal of Materials Chemistry, 2004. 14(12): p. 1795-1797.
16. Norman, T.J., C.D. Grant, D. Magana, J.Z. Zhang, J. Liu, D. Cao, F. Bridges, and A. Van Buuren, Near Infrared Optical Absorption of Gold Nanoparticle Aggregates. The Journal of Physical Chemistry B, 2002. 106(28): p. 7005-7012.
17. Malikova, N., I. Pastoriza-Santos, M. Schierhorn, N.A. Kotov, and L.M. Liz-Marzán, Layer-by-Layer Assembled Mixed Spherical and Planar Gold Nanoparticles:  Control of Interparticle Interactions. Langmuir, 2002. 18(9): p. 3694-3697.
18. Sylvestre, J.P., A.V. Kabashin, E. Sacher, M. Meunier, and J.H.T. Luong, Stabilization and Size Control of Gold Nanoparticles during Laser Ablation in Aqueous Cyclodextrins. Journal of the American Chemical Society, 2004. 126(23): p. 7176-7177.
19. Huang, H. and X. Yang, Synthesis of polysaccharide-stabilized gold and silver nanoparticles: a green method. Carbohydrate Research, 2004. 339(15): p. 2627-2631.
20. Mittal, A.K., Y. Chisti, and U.C. Banerjee, Synthesis of metallic nanoparticles using plant extracts. Biotechnol Adv, 2013. 31(2): p. 346-356.
21. Sharma, J., Y. Tai, and T. Imae, Biomodulation Approach for Gold Nanoparticles: Synthesis of Anisotropic to Luminescent Particles. Chemistry – An Asian Journal, 2010. 5(1): p. 70-73.
22. Qian, J., X. Li, M. Wei, X. Gao, Z. Xu, and S. He, Bio-molecule-conjugated fluorescent organically modified silica nanoparticles as optical probes for cancer cell imaging. Optics Express, 2008. 16(24): p. 19568-19578.
23. Li, G., D. Li, L. Zhang, J. Zhai, and E. Wang, One-Step Synthesis of Folic Acid Protected Gold Nanoparticles and Their Receptor-Mediated Intracellular Uptake. Chemistry – A European Journal, 2009. 15(38): p. 9868-9873.
24. Elnakat, H. and M. Ratnam, Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy. Adv Drug Deliv Rev, 2004. 56(8): p. 1067-1084.
25. Matherly, L.H., Z. Hou, and Y. Deng, Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev, 2007. 26(1): p. 111-128.
26. Bharali, D.J., D.W. Lucey, H. Jayakumar, H.E. Pudavar, and P.N. Prasad, Folate-Receptor-Mediated Delivery of InP Quantum Dots for Bioimaging Using Confocal and Two-Photon Microscopy. Journal of the American Chemical Society, 2005. 127(32): p. 11364-11371.
27. Zhang, Y., N. Kohler, and M. Zhang, Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials, 2002. 23(7): p. 1553-1561.
28. Tsai, S.-W., J.W. Liaw, F.Y. Hsu, Y.Y. Chen, M.J. Lyu, and M.H. Yeh, Surface-Modified Gold Nanoparticles with Folic Acid as Optical Probes for Cellular Imaging. Sensors, 2008. 8(10): p. 6660-6673.
29. Wang, R., J. Di, J. Ma, and Z. Ma, Highly sensitive detection of cancer cells by electrochemical impedance spectroscopy. Electrochimica Acta, 2012. 61: p. 179-184.
30. Sun, C., R. Sze, and M. Zhang, Folic acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI. J Biomed Mater Res A, 2006. 78(3): p. 550-557.
31. Manju, S. and K. Sreenivasan, Gold nanoparticles generated and stabilized by water soluble curcumin-polymer conjugate: blood compatibility evaluation and targeted drug delivery onto cancer cells. J Colloid Interface Sci, 2012. 368(1): p. 144-151.
32. Du, Y.Q., X.X. Yang, W.L. Li, J. Wang, and C.Z. Huang, A cancer-targeted drug delivery system developed with gold nanoparticle mediated DNA–doxorubicin conjugates. RSC Advances, 2014. 4(66): p. 34830-34835.
33. Pandey, S., A. Mewada, M. Thakur, R. Shah, G. Oza, and M. Sharon, Biogenic gold nanoparticles as fotillas to fire berberine hydrochloride using folic acid as molecular road map. Mater Sci Eng C Mater Biol Appl, 2013. 33(7): p. 3716-3722.
34. Zhao, S.S., N. Bukar, J.L. Toulouse, D. Pelechacz, R. Robitaille, J.N. Pelletier, and J.F. Masson, Miniature multi-channel SPR instrument for methotrexate monitoring in clinical samples. Biosens Bioelectron, 2015. 64: p. 664-670.
35. Ladino, C.A., R.V.J. Chari, L.A. Bourret, N.L. Kedersha, and V.S. Goldmacher, Folate-maytansinoids: Target-selective drugs of low molecular weight. International Journal of Cancer, 1997. 73(6): p. 859-864.
36. Atkinson, S.F., T. Bettinger, L.W. Seymour, J.P. Behr, and C.M. Ward, Conjugation of folate via gelonin carbohydrate residues retains ribosomal-inactivating properties of the toxin and permits targeting to folate receptor positive cells. J Biol Chem, 2001. 276(30): p. 27930-27935.
37. Leamon, C.P., M.A. Parker, I.R. Vlahov, L.C. Xu, J.A. Reddy, M. Vetzel, and N. Douglas, Synthesis and Biological Evaluation of EC20:  A New Folate-Derived, 99mTc-Based Radiopharmaceutical. Bioconjugate Chemistry, 2002. 13(6): p. 1200-1210.
38. John, C., B. Linda, P.M. Edgar, and M. Fernando, Photochemical Synthesis of the Bioconjugate Folic Acid-Gold Nanoparticles. Nanomaterials and Nanotechnology, 2013. 3(18): p. 1-6.
39. Zhang, Z., J. Jia, Y. Ma, J. Weng, Y. Sun, and L. Sun, Microwave-assisted one-step rapid synthesis of folic acid modified gold nanoparticles for cancer cell targeting and detection. MedChemComm, 2011. 2(11): p. 1079-1082.
40. Sokolov, K., D. Nida, M. Descour, A. Lacy, M. Levy, B. Hall, S. Dharmawardhane, A. Ellington, B. Korgel, and R. Richards‐Kortum, Molecular Optical Imaging of Therapeutic Targets of Cancer, in Advances in Cancer Research. 2006, Academic Press. p. 299-344.
41. El-Sayed, I.H., X. Huang, and M.A. El-Sayed, Surface Plasmon Resonance Scattering and Absorption of anti-EGFR Antibody Conjugated Gold Nanoparticles in Cancer Diagnostics:  Applications in Oral Cancer. Nano Letters, 2005. 5(5): p. 829-834.
42. Veiseh, O., C. Sun, J. Gunn, N. Kohler, P. Gabikian, D. Lee, N. Bhattarai, R. Ellenbogen, R. Sze, A. Hallahan, J. Olson, and M. Zhang, Optical and MRI Multifunctional Nanoprobe for Targeting Gliomas. Nano Letters, 2005. 5(6): p. 1003-1008.
43. Zhao, W., M.A. Brook, and Y. Li, Design of Gold Nanoparticle-Based Colorimetric Biosensing Assays. ChemBioChem, 2008. 9(15): p. 2363-2371.
44. Karhanek, M., J.T. Kemp, N. Pourmand, R.W. Davis, and C.D. Webb, , Single DNA Molecule Detection Using Nanopipettes and Nanoparticles. Nano Letters, 2005. 5(2): p. 403-407.
45. Taton, T.A., G. Lu, and C.A. Mirkin, Two-Color Labeling of Oligonucleotide Arrays via Size-Selective Scattering of Nanoparticle Probes. Journal of the American Chemical Society, 2001. 123(21): p. 5164-5165.
46. De, M., P.S. Ghosh, and V.M. Rotello, Applications of Nanoparticles in Biology. Advanced Materials, 2008. 20(22): p. 4225-4241.
47. Paciotti, G.F., L. Myer, D. Weinreich, D. Goia, N. Pavel, R.E. McLaughlin, and L. Tamarkin, Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug Deliv, 2004. 11(3): p. 169-183.
48. Kruth, H.S., N.L. Jones, W. Huang, B. Zhao, I. Ishii, J. Chang, C. A. Combs, D. Malide, and W.Y. Zhang, Macropinocytosis is the endocytic pathway that mediates macrophage foam cell formation with native low density lipoprotein. J Biol Chem, 2005. 280(3): p. 2352-2360.
49. Yen, H.J., S.H. Hsu, and C.L. Tsai, Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small, 2009. 5(13): p. 1553-1561.
50. Dixit, V., J. Van den Bossche, D.M. Sherman, D.H. Thompson, and R.P. Andres, Synthesis and Grafting of Thioctic Acid−PEG−Folate Conjugates onto Au Nanoparticles for Selective Targeting of Folate Receptor-Positive Tumor Cells. Bioconjugate Chemistry, 2006. 17(3): p. 603-609.
51. Hilgenbrink, A.R. and P.S. Low, Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci, 2005. 94(10): p. 2135-2146.
52. Marsh, M. and H.T. McMahon, The Structural Era of Endocytosis. Science, 1999. 285(5425): p. 215-220.
53. Liu, Y., D.C. Wu, W.D. Zhang, X. Jiang, C.B. He, T.S. Chung, S.H. Goh, and K.W. Leong, Polyethylenimine-grafted multiwalled carbon nanotubes for secure noncovalent immobilization and efficient delivery of DNA. Angew Chem Int Ed Engl, 2005. 44(30): p. 4782-4785.
54. Kam, N.W., Z. Liu, and H. Dai, Carbon nanotubes as intracellular transporters for proteins and DNA: an investigation of the uptake mechanism and pathway. Angew Chem Int Ed Engl, 2006. 45(4): p. 577-581.
55. Chithrani, B.D., A.A. Ghazani, and W.C.W. Chan, Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells. Nano Letters, 2006. 6(4): p. 662-668.
56. Gao, H., W. Shi, and L.B. Freund, Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci U S A, 2005. 102(27): p. 9469-9474.
57. Tsoli, M., H. Kuhn, W. Brandau, H. Esche, and G. Schmid, Cellular Uptake and Toxicity of Au55 Clusters. Small, 2005. 1(8-9): p. 841-844.
58. Pernodet, N.X.F., Y. Sun, A. Bakhtina, A. Ramakrishnan, J. Sokolov, A. Ulman, and M. Rafailovich, Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. Small, 2006. 2(6): p. 766-773.
59. Pan, Y., S. Neuss, A. Leifert, M. Fischler, F. Wen, U. Simon, and G. Schmid, Size-dependent cytotoxicity of gold nanoparticles. Small, 2007. 3(11): p. 1941-1949.
60. Pan, Y., A. Leifert, D. Ruau, S. Neuss, J. Bornemann, G. Schmid, W. Brandau, U. Simon, and W. Jahnen-Dechent, Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small, 2009. 5(18): p. 2067-2076.
61. Cui, W., J. Li, Y. Zhang, and L. Jiang, Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth. Nanomedicine, 2012. 8(1): p. 46-53.
62. Khlebtsov, N.G. and L.A. Dykman, Optical properties and biomedical applications of plasmonic nanoparticles. Journal of Quantitative Spectroscopy and Radiative Transfer, 2010. 111(1): p. 1-35.
63. Mu, Q., D.L. Broughton, and B. Yan, Endosomal Leakage and Nuclear Translocation of Multiwalled Carbon Nanotubes: Developing a Model for Cell Uptake. Nano Letters, 2009. 9(12): p. 4370-4375.
64. Aubin-Tam, M.E. and K. Hamad-Schifferli, Gold Nanoparticle−Cytochrome c Complexes:  The Effect of Nanoparticle Ligand Charge on Protein Structure. Langmuir, 2005. 21(26): p. 12080-12084.
65. Cho, E.C., J. Xie, P.A. Wurm, and Y. Xia, Understanding the Role of Surface Charges in Cellular Adsorption versus Internalization by Selectively Removing Gold Nanoparticles on the Cell Surface with a I2/KI Etchant. Nano Letters, 2009. 9(3): p. 1080-1084.
66. Goodman, C.M., C.D. McCusker, T. Yilmaz, and V.M. Rotello, Toxicity of Gold Nanoparticles Functionalized with Cationic and Anionic Side Chains. Bioconjugate Chemistry, 2004. 15(4): p. 897-900.
67. Hauck, T.S., A.A. Ghazani, and W.C. Chan, Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. Small, 2008. 4(1): p. 153-159.
68. Lin, J., H. Zhang, Z. Chen, and Y. Zheng, Penetration of Lipid Membranes by Gold Nanoparticles: Insights into Cellular Uptake, Cytotoxicity, and Their Relationship. ACS Nano, 2010. 4(9): p. 5421-5429.
69. Connor, E.E., J. Mwamuka, A. Gole, C.J. Murphy, and M.D. Wyatt, Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small, 2005. 1(3): p. 325-327.
70. Shukla, R., V. Bansal, M. Chaudhary, A. Basu, R.R. Bhonde, and M. Sastry, Biocompatibility of Gold Nanoparticles and Their Endocytotic Fate Inside the Cellular Compartment: A Microscopic Overview. Langmuir, 2005. 21(23): p. 10644-10654.
71. Lewinski, N., V. Colvin, and R. Drezek, Cytotoxicity of nanoparticles. Small, 2008. 4(1): p. 26-49.
72. Thomas, M. and A.M. Klibanov, Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells. Proceedings of the National Academy of Sciences, 2003. 100(16): p. 9138-9143.
73. Tkachenko, A.G., H. Xie, D. Coleman, W. Glomm, J. Ryan, M.F. Anderson, S. Franzen, and D.L. Feldheim, Multifunctional Gold Nanoparticle−Peptide Complexes for Nuclear Targeting. Journal of the American Chemical Society, 2003. 125(16): p. 4700-4701.
74. Tkachenko, A.G., H. Xie, Y. Liu, D. Coleman, J. Ryan, W.R. Glomm, M.K. Shipton, S. Franzen, and D.L. Feldheim, Cellular Trajectories of Peptide-Modified Gold Particle Complexes:  Comparison of Nuclear Localization Signals and Peptide Transduction Domains. Bioconjugate Chemistry, 2004. 15(3): p. 482-490.
75. Fu, W., Shenoy, D.J. Li, C. Crasto, G. Jones, C. Dimarzio, S. Sridhar, and M. Amiji, Biomedical Applications of Gold Nanoparticles Functionalized Using Hetero-Bifunctional Poly(ethylene glycol) Spacer. MRS Online Proceedings Library Archive, 2004. 845: p. 1-6.
76. Murphy, C.J., A.M. Gole, J.W. Stone, P.N. Sisco, E.C. Goldsmith, and S.C. Baxter, Gold Nanoparticles in Biology: Beyond Toxicity to Cellular Imaging. Accounts of Chemical Research, 2008. 41(12): p. 1721-1730.
77. Brannon-Peppas, L. and J.O. Blanchette, Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev, 2004. 56(11): p. 1649-1659.
78. Tong, L., Y. Zhao, T.B. Huff, M.N. Hansen, A. Wei, and J.X. Cheng, Gold Nanorods Mediate Tumor Cell Death by Compromising Membrane Integrity. Adv Mater, 2007. 19: p. 3136-3141.
79. Cole, J.R., N.A. Mirin, M.W. Knight, G.P. Goodrich, and N.J. Halas, Photothermal Efficiencies of Nanoshells and Nanorods for Clinical Therapeutic Applications. The Journal of Physical Chemistry C, 2009. 113(28): p. 12090-12094.
80. Han, M.S., A.K. Lytton-Jean, B.K. Oh, J. Heo, and C.A. Mirkin, Colorimetric screening of DNA-binding molecules with gold nanoparticle probes. Angew Chem Int Ed Engl, 2006. 45(11): p. 1807-1810.
81. Oh, E., M.Y. Hong, D. Lee, S.H. Nam, H.C. Yoon, and H.S. Kim, Inhibition Assay of Biomolecules based on Fluorescence Resonance Energy Transfer (FRET) between Quantum Dots and Gold Nanoparticles. Journal of the American Chemical Society, 2005. 127(10): p. 3270-3271.
82. Katz, E., I. Willner, and J. Wang, Electroanalytical and Bioelectroanalytical Systems Based on Metal and Semiconductor Nanoparticles. Electroanalysis, 2004. 16(12): p. 19-44.
83. Aroca, R.F., R.A. Alvarez-Puebla, N. Pieczonka, S. Sanchez-Cortez, and J.V. Garcia-Ramos, Surface-enhanced Raman scattering on colloidal nanostructures. Adv Colloid Interface Sci, 2005. 116(1-3): p. 45-61.
84. Raisz, L.G., Physiology and pathophysiology of bone remodelind. Clinical Chemistry, 1999. 45(8): p. 1353-1358.
85. Kostura, L., D.L. Kraitchman, A.M. Mackay, M.F. Pittenger, and J.W.M. Bulte, Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR in Biomedicine, 2004. 17(7): p. 513-517.
86. Andreas, K., R. Georgieva, M. Ladwig, M. Notter, M. Sittinger, and J. Ringe, Highly efficient magnetic stem cell labeling with citrate-coated superparamagnetic iron oxide nanoparticles for MRI tracking. Biomaterials, 2012. 33(18): p. 4515-4525.
87. Caplan, A.I. and S.P. Bruder, Mesenchymal stem cells: building blocks for molecular medicine in the 21st century. Trends in Molecular Medicine, 2001. 7(6): p. 259-264.
88. Stein, G.S., J.B. Lian, J.L. Stein, A.J. VanWijnen, and M. Montecino, Transcriptional control of osteoblast growth and differentiation. Physiological Reviews, 1996. 76(2): p. 593-629.
89. Ohgushi, H., S. Tamai, Y. Dohi, S. Tabata, and Y. Suwa, In vitro bone formation by rat marrow cell culture. Journal of Biomedical Materials Research, 1996. 32(3): p. 333-340.
90. Richard, L.M., Raman Spectroscopy for Chemical Analysis. Measurement Science and Technology, 2001. 12(5): p. 653.
91. Stewart, S., D.A. Shea, C.P. Tarnowski, M.D. Morris, D. Wang, R. Franceschi, D.L. Lin, and E. Keller, Trends in early mineralization of murine calvarial osteoblastic cultures: a Raman microscopic study. Journal of Raman Spectroscopy, 2002. 33(7): p. 536-543.
92. Fleischman, M., P. Hendra, and A. McQuillan, Surface-enhanced Raman scattering from silver particles on polymer-replica substrates. Chem Phys Lett, 1974. 26: p. 123.
93. Jeanmaire, D.L. and R.P. Van Duyne, Surface Raman spectroelectrochemistry: Part I. Heterocyclic, aromatic, and aliphatic amines adsorbed on the anodized silver electrode. Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, 1977. 84(1): p. 1-20.
94. Moskovits, M., Surface roughness and the enhanced intensity of Raman scattering by molecules adsorbed on metals. The Journal of Chemical Physics, 2008. 69(9): p. 4159-4161.
95. Koglin, E., J. Sequaris, and P. Valenta, Surface Raman spectra of nucleic acid components adsorbed at a silver electrode. Journal of Molecular Structure, 1980. 60: p. 421-425.
96. Cotton, T.M., S.G. Schultz, and R.P. Van Duyne, Surface-enhanced resonance Raman scattering from water-soluble porphyrins adsorbed on a silver electrode. Journal of the American Chemical Society, 1982. 104(24): p. 6528-6532.
97. Holt, R.E. and T.M. Cotton, Free flavin interference in surface enhanced resonance Raman spectroscopy of glucose oxidase. Journal of the American Chemical Society, 1987. 109(6): p. 1841-1845.
98. Kneipp, K., Y. Wang, H. Kneipp, and I. Itzkan, Population Pumping of Excited Vibrational States by Spontaneous Surface-Enhanced Raman Scattering. Physical Review Letters, 1996. 76(14): p. 2444-2447.
99. Kneipp, K., H. Kneipp, G. Deinum, I. Itzkan,R.R. Dasari, and M.S. Feld, Single-Molecule Detection of a Cyanine Dye in Silver Colloidal Solution Using Near-Infrared Surface-Enhanced Raman Scattering. Applied Spectroscopy, 1998. 52(2): p. 175-178.
100. Schulze, H.G., M.W. Blades, B.B. Gorzalka, L.S. Greek, and R.F.B. Turner, Characteristics of Backpropagation Neural Networks Employed in the Identification of Neurotransmitter Raman Spectra. Applied Spectroscopy, 1994. 48(1): p. 50-57.
101. Westerink, B.H.C., G. Damsma, H. Rollema, J.B. De Vries, and A.S. Horn, Scope and limitations of in vivo brain dialysis: A comparison of its application to various neurotransmitter systems. Life Sciences, 1987. 41(15): p. 1763-1776.
102. Kneipp, K., A.S. Haka, H. Kneipp, K. Badizadegan, and N. Yoshizawa, Surface-Enhanced Raman Spectroscopy in Single Living Cells Using Gold Nanoparticles. Applied Spectroscopy, 2002. 56(2): p. 150-154.
103. Kim, B. and W.M. Sigmund, Functionalized Multiwall Carbon Nanotube/Gold Nanoparticle Composites. Langmuir, 2004. 20(19): p. 8239-8242.
104. Hanaor, D., M. Michelazzi, C. Leonelli, and C.C. Sorrell, The effects of carboxylic acids on the aqueous dispersion and electrophoretic deposition of ZrO2. Journal of the European Ceramic Society, 2012. 32(1): p. 235-244.
105. 蘇淵明(2010)。探討奈米金粒子對類骨細胞行為的影響。國立台灣科技大學化學工程系碩士論文,已出版,台北。.
106. 賴承賦(2014)。分析奈米金粒子之細胞攝入生物相容性與骨傳導性以應用於表面增強拉曼散射。國立台灣科技大學化學工程系碩士論文,已出版,台北。.
107. Albanese, A. and W.C.W. Chan, Effect of Gold Nanoparticle Aggregation on Cell Uptake and Toxicity. ACS Nano, 2011. 5(7): p. 5478-5489.
108. Ross, J.F., P.K. Chaudhuri, and M. Ratnam, Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications. Cancer, 1994. 73(9): p. 2432-2443.
109. Brigger, I., C. Dubernet, and P. Couvreur, Nanoparticles in cancer therapy and diagnosis. Advanced Drug Delivery Reviews, 2002. 54(5): p. 631-651.
110. Hillaireau, H. and P. Couvreur, Nanocarriers' entry into the cell: relevance to drug delivery. Cell Mol Life Sci, 2009. 66(17): p. 2873-96.
111. Zhao, H. and L.Y. Yung, Selectivity of folate conjugated polymer micelles against different tumor cells. Int J Pharm, 2008. 349(1-2): p. 256-268.
112. Chen, M.S., C.Y. Liu, and W.T. Wang, Probing Real-Time Response to Multitargeted Tyrosine Kinase Inhibitor 4-N-(3′-Bromo-Phenyl) Amino-6, 7-Dimethoxyquinazoline in Single Living Cells Using Biofuntionalized Quantum Dots. Journal of Nanomedicine & Nanotechnology, 2011. 02(06): p. 1-7.
113. Paulos, C.M., J.A. Reddy, C.P. Leamon, M.J. Turk, and P.S. Low, Ligand Binding and Kinetics of Folate Receptor Recycling in Vivo: Impact on Receptor-Mediated Drug Delivery. Molecular Pharmacology, 2004. 66(6): p. 1406-1414.
114. Chen, C.S., M. Mrksich, S. Huang, G.M. Whitesides, and D.E. Ingber, Geometric Control of Cell Life and Death. Science, 1997. 276(5317): p. 1425-1428.
115. Adams, J.C. and F.M. Watt, Regulation of development and differentiation by the extracellular matrix. Development, 1993. 117(4): p. 1183-1198.
116. Richter, L., V. Charwat, C. Jungreuthmayer, F. Bellutti, H. Brueckl, and P. Ertl, Monitoring cellular stress responses to nanoparticles using a lab-on-a-chip. Lab Chip, 2011. 11(15): p. 2551-2560.
117. Liu, D., J.C. Zhang, and C.Q. Yi, The effects of gold nanoparticles on the proliferation, differentiation, and mineralization function of MC3T3-E1 cells in vitro. Chinese Science Bulletin, 2010. 55(11): p. 1013-1019.
118. Ko, W.K., D.N. Heo, and S.J. Lee, The effect of gold nanoparticle size on osteogenic differentiation of adipose-derived stem cells. Journal of Colloid and Interface Science, 2015. 438: p. 68-76.
119. Taton, T.A., Nanotechnology: Boning up on biology. Nature, 2001. 412(6846): p. 491-492.
120. Hanlon, E.B., K.E. Shafer, and J.T. Motz, Prospects for in vivo Raman spectroscopy. Physics in Medicine and Biology, 2000. 45(2): p. 1-59.
121. Dong, J., Y. Li, and M. Zhang, Ultrasensitive surface-enhanced Raman scattering detection of alkaline phosphatase. Analytical Methods, 2014. 6(22): p. 9168-9172.
122. Usta, D.D., K. Salimi, A. Pinar, İ. Coban, T. Tekinay, and A. Tuncel, A Boronate Affinity-Assisted SERS Tag Equipped with a Sandwich System for Detection of Glycated Hemoglobin in the Hemolysate of Human Erythrocytes. ACS Applied Materials & Interfaces, 2016. 8(19): p. 11934-11944.

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