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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林?輝(Feng-Huei Lin) | |
dc.contributor.author | Min-Hua Chen | en |
dc.contributor.author | 陳民樺 | zh_TW |
dc.date.accessioned | 2021-06-16T03:36:58Z | - |
dc.date.available | 2018-08-11 | |
dc.date.copyright | 2015-08-11 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-05-26 | |
dc.identifier.citation | 1. Xu ZP, Zeng QH, Lu GQ, Yu AB: Inorganic nanoparticles as carriers for efficient cellular delivery. Chem Engi Sci 2006, 61:1027-1040.
2. Kodama K, Katayama Y, Shoji Y, Nakashima H: The features and shortcomings for gene delivery of current non-viral carriers. Curr Med Chem 2006, 13:2155-2161. 3. Nelson CE, Kintzing JR, Hanna A, Shannon JM, Gupta MK, Duvall CL: Balancing cationic and hydrophobic content of PEGylated siRNA polyplexes enhances endosome escape, stability, blood circulation time, and bioactivity in vivo. ACS Nano 2013, 7:8870-8880. 4. Guo X, Huang L: Recent advances in nonviral vectors for gene delivery. Acc Chem Res 2012, 45:971-979. 5. Kim T, Hyeon T: Applications of inorganic nanoparticles as therapeutic agents. Nanotechnology 2014, 25:012001. 6. Sun J, Chao J, Huang J, Yin M, Zhang H, Peng C, Zhong Z, Chen N: Uniform small graphene oxide as an efficient cellular nanocarrier for immunostimulatory CpG oligonucleotides. ACS Appl Mater Interfaces 2014, 6:7926-7932. 7. Oh N, Park J-H: Endocytosis and exocytosis of nanoparticles in mammalian cells. Int J Nanomedicine 2014, 9:51-63. 8. Liu DM, Troczynski T, Tseng WJ: Water-based sol-gel synthesis of hydroxyapatite: process development. Biomaterials 2001, 22:1721-1730. 9. Sanjuan MA, Rao N, Lai KT, Gu Y, Sun S, Fuchs A, Fung-Leung WP, Colonna M, Karlsson L: CpG-induced tyrosine phosphorylation occurs via a TLR9-independent mechanism and is required for cytokine secretion. J Cell Biol 2006, 172:1057-1068. 10. Jahrsdorfer B, Weiner GJ: CpG oligodeoxynucleotides as immunotherapy in cancer. Update Cancer Ther 2008, 3:27-32. 11. Hanagata N: Recognition of Oligodeoxynucleotides by Toll-like Receptor 9: Phosphodiester Backbone vs. Phosphorothioate Backbone and Monomer vs. Multimer. Nano Biomed 2013, 5:55-63. 12. Hanagata N: Structure-dependent immunostimulatory effect of CpG oligodeoxynucleotides and their delivery system. Int J Nanomedicine 2012, 7:2181-2195. 13. Chinnathambi S, Chen S, Ganesan S, Hanagata N: Binding mode of CpG oligodeoxynucleotides to nanoparticles regulates bifurcated cytokine induction via Toll-like receptor 9. Sci Rep 2012, 2:534. 14. Khosravi-Darani K, Mozafari MR, Rashidi L, Mohammadi M: Calcium based non-viral gene delivery: an overview of methodology and applications. Acta Med Iran 2010, 48:133-141. 15. Lee D, Upadhye K, Kumta PN: Nano-sized calcium phosphate (CaP) carriers for non-viral gene deilvery. Mater Sci Eng B 2012, 177:289-302. 16. Kalita SJ, Bhardwaj A, Bhatt HA: Nanocrystalline calcium phosphate ceramics in biomedical engineering. Mater Sci Eng C 2007, 27:441-449. 17. Chen M-H, Yoshioka T, Ikoma T, Hanagata N, Lin F-H, Tanaka J: Photoluminescence and doping mechanism of theranostic Eu3+/Fe3+dual-doped hydroxyapatite nanoparticles. Sci Technol Adv Mater 2014, 15:055005. 18. Ciobanu CS, Iconaru SL, Pasuk I, Vasile BS, Lupu AR, Hermenean A, Dinischiotu A, Predoi D: Structural properties of silver doped hydroxyapatite and their biocompatibility. Mater Sci Eng C Mater Biol Appl 2013, 33:1395-1402. 19. Chandra VS, Baskar G, Suganthi RV, Elayaraja K, Joshy MI, Beaula WS, Mythili R, Venkatraman G, Kalkura SN: Blood compatibility of iron-doped nanosize hydroxyapatite and its drug release. ACS Appl Mater Interfaces 2012, 4:1200-1210. 20. Hou CH, Hou SM, Hsueh YS, Lin J, Wu HC, Lin FH: The in vivo performance of biomagnetic hydroxyapatite nanoparticles in cancer hyperthermia therapy. Biomaterials 2009, 30:3956-3960. 21. Hui J, Zhang X, Zhang Z, Wang S, Tao L, Wei Y, Wang X: Fluoridated HAp:Ln3+ (Ln = Eu or Tb) nanoparticles for cell-imaging. Nanoscale 2012, 4:6967-6970. 22. Huang S, Zhu J, Zhou K: Effects of Eu3+ ions on the morphology and luminescence properties of hydroxyapatite nanoparticles synthesized by one-step hydrothermal method. Mater Res Bull 2012, 47:24-28. 23. Eruslanov E, Kusmartsev S: Identification of ROS using oxidized DCFDA and flow-cytometry. Methods Mol Biol 2010, 594:57-72. 24. Dotan Y, Lichtenberg D, Pinchuk I: Lipid peroxidation cannot be used as a universal criterion of oxidative stress. Prog Lipid Res 2004, 43:200-227. 25. Ozben T: Oxidative stress and apoptosis: impact on cancer therapy. J Pharm Sci 2007, 96:2181-2196. 26. Han Y, Chen JZ: Oxidative stress induces mitochondrial DNA damage and cytotoxicity through independent mechanisms in human cancer cells. Biomed Res Int 2013:825065. 27. Robertson CA, Evans DH, Abrahamse H: Photodynamic therapy (PDT): a short review on cellular mechanisms and cancer research applications for PDT. J Photochem Photobiol B 2009, 96:1-8. 28. Klein S, Dell'Arciprete ML, Wegmann M, Distel LV, Neuhuber W, Gonzalez MC, Kryschi C: Oxidized silicon nanoparticles for radiosensitization of cancer and tissue cells. Biochem Biophys Res Commun 2013, 434:217-222. 29. Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J: The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine 2013, 9:1-14. 30. Deep Kwatra, Anand Venugopal SA: Nanoparticles in radiation therapy: a summary of various approaches to enhance radiosensitization in cancer. Transl Cancer Res 2013, 2:330-342. 31. Carter JD, Cheng NN, Qu Y, Suarez GD, Guo T: Nanoscale energy deposition by X-ray absorbing nanostructures. J Phys Chem B 2007, 111:11622-11625. 32. POTTIER AS, Borghi E, Levy L: New use of metals as nanosized radioenhancers. Anticancer Res 2014, 34:443-454. 33. Maggiorella L, Barouch G, Devaux C, Pottier As, Deutsch E, Bourhis J, Levy L: Nanoscale radiotherapy with hafnium oxide nanoparticles. Future Oncol 2012, 8:1167-1181. 34. Mendoza JG, Frutis MA, Flores GA, Hipolito MG, Maciel Cerda A, Azorin Nieto J, Montalvo TR, Falcony C: Synthesis and characterization of hafnium oxide films for thermo and photoluminescence applications. Appl Radiat Isot 2010, 68:696-699. 35. Bae YM, Park YI, Nam SH, Kim JH, Lee K, Kim HM, Yoo B, Choi JS, Lee KT, Hyeon T, Suh YD: Endocytosis, intracellular transport, and exocytosis of lanthanide-doped upconverting nanoparticles in single living cells. Biomaterials 2012, 33:9080-9086. 36. Wang Z, Li N, Zhao J, White JC, Qu P, Xing B: CuO nanoparticle interaction with human epithelial cells: cellular uptake, location, export, and genotoxicity. Chem Res Toxicol 2012, 25:1512-1521. 37. Devanand Venkatasubbu G, Ramasamy S, Ramakrishnan V, Kumar J: Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin. 3 Biotech 2011, 1:173-186. 38. Li Y, Nam CT, Ooi CP: Iron(III) and manganese(II) substituted hydroxyapatite nanoparticles: Characterization and cytotoxicity analysis. J Phys Conf Ser 2009, 187:012024. 39. Chen F, Huang P, Zhu YJ, Wu J, Cui DX: Multifunctional Eu3+/Gd3+ dual-doped calcium phosphate vesicle-like nanospheres for sustained drug release and imaging. Biomaterials 2012, 33:6447-6455. 40. Huang G, Chen H, Dong Y, Luo X, Yu H, Moore Z, Bey EA, Boothman DA, Gao J: Superparamagnetic iron oxide nanoparticles: amplifying ROS stress to improve anticancer drug efficacy. Theranostics 2013, 3:116-126. 41. M. P. Ferraz, F. J. Monterio, Manuel CM: Hydroxyapatite nanoparticles: A review of preparation methodologies. J Appl Biomater Biomech 2004, 2:74-80. 42. Jiang M, Terra J, Rossi A, Morales M, Baggio Saitovitch E, Ellis D: Fe2+/Fe3+ substitution in hydroxyapatite: Theory and experiment. Phys Rev B 2002, 66:224107. 43. Fox K, Tran PA, Tran N: Recent advances in research applications of nanophase hydroxyapatite. Chemphyschem 2012, 13:2495-2506. 44. Okada M, Furuzono T: Hydroxylapatite nanoparticles: fabrication methods and medical applications. Sci Technol Adv Mat 2012, 13:064103. 45. Bhupinder Singh LL: Calcium Phosphate Nanoparticles and their Biomedical Potential. J Nanomater Mol Nanotechnol 2015, 4:1000154. 46. Uddin MH, Matsumoto T, Okazaki M, Nakahira A, Sohmura T: Biomimetic fabrication of apatite related biomaterials. Biomim Learn Nat 2010:289-304. 47. Vollmer J, Krieg AM: Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv Drug Deliv Rev 2009, 61:195-204. 48. Klinman DM: Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol 2004, 4:249-258. 49. Abel K, Wang Y, Fritts L, Sanchez E, Chung E, Fitzgerald-Bocarsly P, Krieg AM, Miller CJ: Deoxycytidyl-deoxyguanosine oligonucleotide classes A, B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells. Clin Diagn Lab Immunol 2005, 12:606-621. 50. Krieg AM: CpG motifs: the active ingredient in bacterial extracts? Nat Med 2003, 9:831-835. 51. Weiss JM, Subleski JJ, Wigginton JM, Wiltrout RH: Immunotherapy of cancer by IL-12-based cytokine combinations. Expert Opin Biol Ther 2007, 7:1705-1721. 52. Colombo MP, Trinchieri G: Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002, 13:155-168. 53. Zhang Y, Palmer GH, Abbott JR, Howard CJ, Hope JC, Brown WC: CpG ODN 2006 and IL-12 are comparable for priming Th1 lymphocyte and IgG responses in cattle immunized with a rickettsial outer membrane protein in alum. Vaccine 2003, 21:3307-3318. 54. Tampieri A, D'Alessandro T, Sandri M, Sprio S, Landi E, Bertinetti L, Panseri S, Pepponi G, Goettlicher J, Banobre-Lopez M, Rivas J: Intrinsic magnetism and hyperthermia in bioactive Fe-doped hydroxyapatite. Acta Biomater 2012, 8:843-851. 55. Wu HC, Wang TW, Sun JS, Wang WH, Lin FH: A novel biomagnetic nanoparticle based on hydroxyapatite. Nanotechnology 2007, 18:165601. 56. Hou CH, Chen CW, Hou SM, Li YT, Lin FH: The fabrication and characterization of dicalcium phosphate dihydrate-modified magnetic nanoparticles and their performance in hyperthermia processes in vitro. Biomaterials 2009, 30:4700-4707. 57. Wang TW, Wu HC, Wang WR, Lin FH, Lou PJ, Shieh MJ, Young TH: The development of magnetic degradable DP-Bioglass for hyperthermia cancer therapy. J Biomed Mater Res A 2007, 83:828-837. 58. G. A. Gamal, F. A. Al-Mufadi, Said AH: Effect of Iron Additives on the Microstructure of Hydroxyapatite. Eng Technol Appl Sci Res 2013, 3:532-539. 59. Miyaji F, Kono Y, Suyama Y: Formation and structure of zinc-substituted calcium hydroxyapatite. Mater Res Bull 2005, 40:209-220. 60. Webster TJ, Massa-Schlueter EA, Smith JL, Slamovich EB: Osteoblast response to hydroxyapatite doped with divalent and trivalent cations. Biomaterials 2004, 25:2111-2121. 61. Borum-Nicholas L, Wilson OC, Jr.: Surface modification of hydroxyapatite. Part I. Dodecyl alcohol. Biomaterials 2003, 24:3671-3679. 62. Graeve OA, Kanakala R, Madadi A, Williams BC, Glass KC: Luminescence variations in hydroxyapatites doped with Eu2+ and Eu3+ ions. Biomaterials 2010, 31:4259-4267. 63. Hasna K, Kumar SS, Komath M, Varma MR, Jayaraj MK, Kumar KR: Synthesis of chemically pure, luminescent Eu3+ doped HAp nanoparticles: a promising fluorescent probe for in vivo imaging applications. Phys Chem Chem Phys 2013, 15:8106-8111. 64. Yang P, Deng P, Yin Z: Concentration quenching in Yb:YAG. Journal of Luminescence 2002, 97:51-54. 65. Andre RS, Paris EC, Gurgel MFC, Rosa ILV, Paiva-Santos CO, Li MS, Varela JA, Longo E: Structural evolution of Eu-doped hydroxyapatite nanorods monitored by photoluminescence emission. J Alloy Compd 2012, 531:50-54. 66. Chen XY, Liu GK: The standard and anomalous crystal-field spectra of Eu3+. J Solid State Chem 2005, 178:419-428. 67. Kikuchi M, Matsumoto HN, Yamada T, Koyama Y, Takakuda K, Tanaka J: Glutaraldehyde cross-linked hydroxyapatite/collagen self-organized nanocomposites. Biomaterials 2004, 25:63-69. 68. Chowdhury EH, Maruyama A, Kano A, Nagaoka M, Kotaka M, Hirose S, Kunou M, Akaike T: pH-sensing nano-crystals of carbonate apatite: effects on intracellular delivery and release of DNA for efficient expression into mammalian cells. Gene 2006, 376:87-94. 69. Brundin M, Figdor D, Sundqvist G, Sjogren U: DNA binding to hydroxyapatite: a potential mechanism for preservation of microbial DNA. J Endod 2013, 39:211-216. 70. Min Jiang, Chen G: High Ca2+-phosphate transfection efficiency in low-density neuronal cultures. Nat Protoc 2006, 1:695-700. 71. Elangovan S, Jain S, Tsai PC, Margolis HC, Amiji M: Nano-sized calcium phosphate particles for periodontal gene therapy. J Periodontol 2013, 84:117-125. 72. Lebon C, Villalpando Rodriguez G, El Zaoui I, Jaadane I, Behar-Cohen F, Torriglia A: On the use of an appropriate TUNEL assay to identify apoptotic cells. Anal Biochem 2015. 73. Nagai A, Tanaka K, Tanaka Y, Nakamura M, Hashimoto K, Yamashita K: Electric polarization and mechanism of B-type carbonated apatite ceramics. J Biomed Mater Res A 2011, 99:116-124. 74. Hadeel A, Jeffrey LE, Ramin R, Hans C, Fariba D: Preparation of Nanostructured Hydroxyapatite in Organic Solvents for Clinical Applications. Trends Biomater Artif Organs 2011, 25:12-19. 75. Syed Sibte Asghar ABIDI, MURTAZA Q: Synthesis and Characterization of Nano-hydroxyapatite Powder Using Wet Chemical Precipitation Reaction. J Mater Sci Technol 2014, 30. 76. Zhou R, Si S, Zhang Q: Water-dispersible hydroxyapatite nanoparticles synthesized in aqueous solution containing grape seed extract. Appl Surf Sci 2012, 258:3578-3583. 77. Junjun Tan, Minfang Chen, Xia J: Water-dispersible hydroxyapatite nanorods synthesized by a facile method. Appl Surf Sci 2009, 255:8774-8779. 78. Martins MA, Santos C, Almeida MM, Costa ME: Hydroxyapatite micro- and nanoparticles: nucleation and growth mechanisms in the presence of citrate species. J Colloid Interface Sci 2008, 318:210-216. 79. Chen N, Wei M, Sun Y, Li F, Pei H, Li X, Su S, He Y, Wang L, Shi J, et al: Self-assembly of poly-adenine-tailed CpG oligonucleotide-gold nanoparticle nanoconjugates with immunostimulatory activity. Small 2014, 10:368-375. 80. Tao C, Zhu Y, Xu Y, Zhu M, Morita H, Hanagata N: Mesoporous silica nanoparticles for enhancing the delivery efficiency of immunostimulatory DNA drugs. Dalton Trans 2014, 43:5142-5150. 81. de Chickera S, Willert C, Mallet C, Foley R, Foster P, Dekaban GA: Cellular MRI as a suitable, sensitive non-invasive modality for correlating in vivo migratory efficiencies of different dendritic cell populations with subsequent immunological outcomes. Int Immunol 2012, 24:29-41. 82. Zhao D, Alizadeh D, Zhang L, Liu W, Farrukh O, Manuel E, Diamond DJ, Badie B: Carbon nanotubes enhance CpG uptake and potentiate antiglioma immunity. Clin Cancer Res 2011, 17:771-782. 83. Stayton I, Winiarz J, Shannon K, Ma Y: Study of uptake and loss of silica nanoparticles in living human lung epithelial cells at single cell level. Anal Bioanal Chem 2009, 394:1595-1608. 84. Ahmad-Nejad P, Hacker H, Rutz M, Bauer S, Vabulas RM, Wagner H: Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol 2002, 32:1958-1968. 85. Wu YJ, Tsai TW, Huang SJ, Mou Y, Lin CJ, Chan JC: Hydrogen bond formation between citrate and phosphate ions in spherulites of fluorapatite. Langmuir 2013, 29:11681-11686. 86. Okazaki M, Yoshida Y, Yamaguchi S, Kaneno M, Elliott JC: Affinity binding phenomena of DNA onto apatite crystals. Biomaterials 2001, 22:2459-2464. 87. Shirota Y, Shirota H, Klinman DM: Intratumoral injection of CpG oligonucleotides induces the differentiation and reduces the immunosuppressive activity of myeloid-derived suppressor cells. J Immunol 2012, 188:1592-1599. 88. Joshi VB, Geary SM, Salem AK: Biodegradable particles as vaccine delivery systems: size matters. AAPS J 2013, 15:85-94. 89. Jones LL, Vignali DA: Molecular interactions within the IL-6/IL-12 cytokine/receptor superfamily. Immunol Res 2011, 51:5-14. 90. Wu CC, Lee J, Raz E, Corr M, Carson DA: Necessity of oligonucleotide aggregation for toll-like receptor 9 activation. J Biol Chem 2004, 279:33071-33078. 91. Rutz M, Metzger J, Gellert T, Luppa P, Lipford GB, Wagner H, Bauer S: Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur J Immunol 2004, 34:2541-2550. 92. Maitra A: Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy. Expert Rev Mol Diagn 2005, 5:893-905. 93. Lemos H, Huang L, McGaha TL, Mellor AL: Cytosolic DNA sensing via the stimulator of interferon genes adaptor: Yin and Yang of immune responses to DNA. Eur J Immunol 2014. 94. Yang P, An H, Liu X, Wen M, Zheng Y, Rui Y, Cao X: The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway. Nat Immunol 2010, 11:487-494. 95. Xia Zhang, Justin P. Edwards a, Mosser DM: The Expression of Exogenous Genes in Macrophages: Obstacles and Opportunities. Methods Mol Biol 2009, 531:123. 96. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM: CpG DNA as a vaccine adjuvant. Expert Rev Vaccines 2011, 10:499-511. 97. Shannon RD: Revised Effective Ionic Radii and Systematic Studies of Interatomie Distances in Halides and Chaleogenides. Acta Crystallogr A 1976, A32. 98. Porter A, Patel N, Brooks R, Best S, Rushton N, Bonfield W: Effect of carbonate substitution on the ultrastructural characteristics of hydroxyapatite implants. J Mater Sci Mater Med 2005, 16:899-907. 99. Uskokovic V, Uskokovic DP: Nanosized hydroxyapatite and other calcium phosphates: chemistry of formation and application as drug and gene delivery agents. J Biomed Mater Res B Appl Biomater 2011, 96:152-191. 100. El-Dakdouki MH, Pure E, Huang X: Development of drug loaded nanoparticles for tumor targeting. Part 2: Enhancement of tumor penetration through receptor mediated transcytosis in 3D tumor models. Nanoscale 2013, 5:3904-3911. 101. Chu S-H, Karri S, Ma Y-B, Feng D-F, Li Z-Q: In vitro and in vivo radiosensitization induced by hydroxyapatite nanoparticles. Neuro-Oncology 2013, 15:880-890. 102. Deghfel B, Kahoul A, Nekkab M: Hafnium to thorium M-shell X-ray production cross sections by proton impact. J Radiat Res Appl Sci 2014, 7:512-518. 103. Stearns RC, Paulauskis JD, Godleski JJ: Endocytosis of ultrafine particles by A549 cells. Am J Respir Cell Mol Biol 2001, 24:108-115. 104. Simon H-U, Haj-Yehia A, Levi-Schaffer F: Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis 2000, 5:415-418. 105. Singh N, Jenkins GJ, Asadi R, Doak SH: Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Rev 2010, 1. 106. Vidrio E, Jung H, Anastasio C: Generation of Hydroxyl Radicals from Dissolved Transition Metals in Surrogate Lung Fluid Solutions. Atmos Environ (1994) 2008, 42:4369-4379. 107. Ramanathan B, Jan KY, Chen CH, Hour TC, Yu HJ, Pu YS: Resistance to paclitaxel is proportional to cellular total antioxidant capacity. Cancer Res 2005, 65:8455-8460. 108. Gabai VL, Yaglom JA, Volloch V, Meriin AB, Force T, Koutroumanis M, Massie B, Mosser DD, Sherman MY: Hsp72-mediated suppression of c-Jun N-terminal kinase is implicated in development of tolerance to caspase-independent cell death. Mol Cell Biol 2000, 20:6826-6836. 109. Haddad JJ: Redox and oxidant-mediated regulation of apoptosis signaling pathways: immuno-pharmaco-redox conception of oxidative siege versus cell death commitment. Int Immunopharmacol 2004, 4:475-493. 110. Alberts WM: Follow up and surveillance of the patient with lung cancer: what do you do after surgery? Respirology 2007, 12:16-21. 111. Sawabata N: Locoregional recurrence after pulmonary sublobar resection of non-small cell lung cancer: can it be reduced by considering cancer cells at the surgical margin? Gen Thorac Cardiovasc Surg 2013, 61:9-16. 112. McMahon SJ, Hyland WB, Muir MF, Coulter JA, Jain S, Butterworth KT, Schettino G, Dickson GR, Hounsell AR, O'Sullivan JM, et al: Nanodosimetric effects of gold nanoparticles in megavoltage radiation therapy. Radiother Oncol 2011, 100:412-416. 113. Shirota H, Klinman DM: Recent progress concerning CpG DNA and its use as a vaccine adjuvant. Expert Rev Vaccines 2014, 13:299-312. 114. Germann T, Bongartz M, Dlugonska H, Hess H, Schmitt E, Kolbe L, Kolsch E, Podlaski FJ, Gately MK, Rude E: Interleukin-12 profoundly up-regulates the synthesis of antigen-specific complement-fixing IgG2a, IgG2b and IgG3 antibody subclasses in vivo. Eur J Immunol 1995, 25:823-829. 115. Welsh RM, Bahl K, Marshall HD, Urban SL: Type 1 interferons and antiviral CD8 T-cell responses. PLoS Pathog 2012, 8:e1002352. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54703 | - |
dc.description.abstract | 由於磷酸鈣陶瓷(calcium phosphate)具有優越的生物相容性、生物活性,與人體骨骼或牙齒組成分類似等特性,因此目前它被視為較合適的骨骼植入物,並在組織工程上有許多應用。近年來已有許多不同結晶相的磷酸鈣陶瓷被應用在生物醫學領域,而其中又以氫氧基磷灰石的應用最為普遍,最廣為人知,這是因為氫氧基磷灰石具有高度穩定性,其材料特性不易受酸鹼值、溫度及生理環境影響而產生變化。
在先前的研究中,我們已觀察到,利用濕式化學沉澱法,結晶性奈米氫氧基磷灰石可在水溶液中合成,而不需要添加任何的介面活性劑。合成出的粒子是屬於B型含碳的氫氧基磷灰石,且能長時間穩定地懸浮在培養液中,這樣的特性非常合適作為生物應用。有這樣令人振奮的結果,且考量到癌症仍是現今社會主要的致死疾病。因此,本研究我們將致力於氫氧基磷灰石奈米顆粒對癌症治療的研究和探討,包括: (1) 以氫氧基磷灰石奈米顆粒攜帶含有胞嘧啶(cytosine)-鳥糞鹼(guanine)雙核苷酸序列模組的寡苷酸(oligodeoxynucleotides; CpG ODN),作為癌症免疫治療的載體。 (2) 藉由參雜四價鉿離子(Hf4+)於氫氧基磷灰石中(Hf:HAp),探討經放射線照射後,作為癌症治療的可行性評估。 在前半部的研究裡,我們利用濕式化學沉澱法,合成帶有CpG ODN的氫氧基磷灰石奈米顆粒。藉由分析其在溶液中的穩定性、顆粒大小、表面型態、CpG ODN載附量、及其刺激免疫細胞產生細胞激素的表現,來評估未來應用於癌症免疫治療的可行性。此部份的研究,我們觀察到結晶性氫氧基磷灰石奈米顆粒可增加CpG ODN在融酶體上的釋放,進而使CpG ODN與Toll-like receptor(TLR9)進行交互作用。相較於非晶型磷酸鈣奈米顆粒及奈米微脂體,結晶性氫氧基磷灰石可促使免疫細胞產生較多的細胞激素(IL-12及IL-6)。這些細胞激素的對未來癌症免疫治療扮演重要角色。 在後半部的研究裡,我們同樣經由式化學沉澱法,合成具有四價鉿離子摻雜的氫氧基磷灰石奈米顆粒。並以人類肺腺癌A549細胞株作為此奈米顆粒在動物體外(in-vitro)及體內(in-vivo)的療效評估。本研究證實摻雜四價鉿離子的氫氧基磷灰石經放射線照射後,可增加細胞內活性氧化物質(reactive oxygen species; ROS)的量並促進細胞凋亡。此研究結果可作為未來治療深層癌細胞的參考,以取代目前光動力治療中,可見光源穿透組織深度的限制。 | zh_TW |
dc.description.abstract | Calcium phosphates, because of their superior biocompatibility, bioactivity and compositionally similar to the mineral phases of the bone, are preferred as bone grafts and tissue engineering. Several phases of calcium phosphate have currently been used in the biomedical field. Among those, HAp, due to the highest stability, is the most popular and well-known phase of calcium phosphate, which is the most stable with the variation of pH, temperature or composition of the physiological fluid. In our preliminary study, we observed crystalline nano-sized HAp could be easily synthesized by wet chemical precipitation in water without addition of any surfactant, showing the particles belonged to biodegradable B type carbonated HAp and could be well-suspended in culture medium for a relatively long period of time, indicating it could be an ideal candidate for biological application. In recent years, cancer treatment has been always a global and imperative health issue. With these encouraging results, in this study, we ask whether functional crystalline HAp can treat cancer, involving (1) Enhancing immune-activation of macrophage by delivering CpG ODN-loaded HAp nanoparticles; (2) Reactive oxygen species (ROS)-enhanced cancer treatment by hafnium-doped HAp nanoparticles with ionizing radiation.
In the first part of our study, we synthesized HAp nanoparticles by wet chemical precipitation method. HAp nanoparticles loaded with CpG ODN were characterized for their stability, size, morphology, loading capacity, and cytokine induction behavior. The results revealed TLR9 dependent cytokine (IL-12 and IL-6) was enhanced by loading CpG ODN onto crystalline HAp nanoparticles, indicating HAp facilitated the retaintion of ODNs in endolysosome, giving rise to specific CpG ODN/ TLR9 interactions. The results suggest HAp may be an appropriate vehicle for ODN delivery and cancer immunotherapy. In the second part, 15% of hafnium ions were successfully doped into HAp crystal by wet chemical precipitation method. The human lung epithelia cell line A549 was selected as the in-vitro and in-vivo model. The results suggest Hf4+-doped HAp nanoparticles enhance the quantity of ROS in cells and induce cell apoptosis by bombarding with ionizing radiation, indicating a possible approach instead of photodynamic therapy to treat deeper tumor. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T03:36:58Z (GMT). No. of bitstreams: 1 ntu-104-D97548011-1.pdf: 40019793 bytes, checksum: cda0597e09f047c970be53bb42926e81 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | 口試委員審定書…………………………………………...……………………………ii
致謝……………………………………………………………………………………..iii 中文摘要…………………………………………………...……………………………v ABSTRACT………………………………………………..…………………………..vii TABLE OF CONTENT……………………………………...…………………………ix LIST OF CHART………………………………………………..…………..…………xii LIST OF TABLES……………………………………………………………….……xvi LIST OF ABBREVIATION………………..……….………………………………..xvii CHAPTER 1 INTRODUCTION………………………………………………….……..1 1.1 Introduction of enhancing immune-activation of macrophage by delivering CpG ODN-loaded HAp nanoparticles.…………...…………………………..4 1.2 Introduction of ROS-enhanced cancer treatment by hafnium-doped HAp nanoparticles with ionizing radiation……………...…….……………………9 CHAPTER 2 THEORETICAL BASIS………….……………...………………...……14 2.1 Hydroxyapatite..………………………………...………………………..….14 2.2 Fate of intracellular delivery of calcium phosphate nanoparticles…...……..16 2.3 TLR9 dependent cytokine as immunotherapy in cancer………………...…..18 2.4 Doping mechanism of HAp nanoparticles.……………….............................23 2.5 Principle of radiosensitization by metallic containing compounds…...….....34 CHAPTER 3 MATERIALS AND METHODS…...……...…………………………....36 3.1 Enhancing immune-activation of macrophage by delivering CpG ODN-loaded HAp nanoparticles…..………………………………………...37 3.1.1 Synthesis of HAp and ODN-loaded HAp particles….…………….37 3.1.2 Characterization of HAp particles……...…………………………..38 3.1.3 Construction of dsCpG ODN and dsODN………………………....39 3.1.4 Characterization of HAp-CpG………...………………….....……...40 3.1.5 Synthesis of ACP-CpG……...……………………………………..41 3.1.6 Cell line…………………………………………………………….42 3.1.7 Cytokine secretion test by qPCR analysis…..…...………….……..42 3.1.8 Imaging of cellular uptake………………………...……………….44 3.1.9 Plasmid preparation and transfection efficiency study…...………...45 3.2 ROS-enhanced cancer treatment by hafnium-doped HAp nanoparticles with ionizing radiation…………………….……………………………………...47 3.2.1 Synthesis of Hf:HAp nanoparticles..………...…………………….47 3.2.2 Characterization of Hf:HAp particles………...……………...……..48 3.2.3 Cell culture………………………………………………………....48 3.2.4 Cellular ROS measurement………………...…………….....……...49 3.2.5 Cell viability and cytotoxicity assay……...………………………..50 3.2.6 In-vivo antitumor efficacy………...……………………………….50 3.2.7 Statistical analysis………..………………………………….……..51 CHAPTER 4 RESULTS AND DISCUSSIONS……...…..…………………………....52 4.1 Enhancing immune-activation of macrophage by delivering CpG ODN-loaded HAp nanoparticles……………………………..……………...52 4.1.1 Characterization of HAp particles………...………………………..52 4.1.2 Loading of CpG ODN onto HAp particles……...………………....59 4.1.3 Cytokine induction by HAp-CpG particles…...………….....……...61 4.1.4 Intracellular localization of HAp-CpG…………...………………..70 4.1.5 IFN-β secretion of particles loaded with dsODN……....……….....73 4.1.6 Transfection efficiency of particles in HeLa cells…...…….………75 4.1.7 Summary…...………………...…………………………………….77 4.2 ROS-enhanced cancer treatment by hafnium-doped HAp nanoparticles with ionizing radiation …………………………………………………………...78 4.2.1 Phase, morphology and composition of Hf:HAp…...…………..….78 4.2.2 In-vitro ROS generation of Hf:HAP nanoparticles with ionizing radiation….……...……………………………………………….....83 4.2.3 In-vitro cytotoxicity of Hf:HAp nanoparticles with ionizing radiation ……...………………………………………………….....87 4.2.4 In-vivo antitumor efficacy………………….....………….....……...89 4.2.5 Summary………………………...……..…………………………..94 CHAPTER 5 CONCLUSION AND FUTURE PROSPECT….……...……..…………95 5.1 Conclusions……………………………………………………………….....95 5.2 Future prospect……………….……………………………………………...97 Reference………………………...……...……………………………………………...99 Curriculum Vitae………………………………...…...…………………..…………...114 Representative writings……………………...………………………………………..122 | |
dc.language.iso | en | |
dc.title | 功能性氫氧基磷灰石奈米顆粒於癌症治療之研究 | zh_TW |
dc.title | Functional Hydroxyapatite Nanoparticles for Cancer
Treatment | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 花方信孝(Hanagata Nobutaka) | |
dc.contributor.oralexamcommittee | 生駒俊元(Toshiyuki Ikoma),林俊彬,陳?平,張國基 | |
dc.subject.keyword | 氫氧基磷灰石,含有CpG雙核?酸序列模組的寡?酸,鉿離子,活性氧化物質, | zh_TW |
dc.subject.keyword | hydroxyapatite,CpG oligodeoxynucleotides,hafnium ions,Reactive oxygen species, | en |
dc.relation.page | 124 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2015-05-27 | |
dc.contributor.author-college | 工學院 | zh_TW |
dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
顯示於系所單位: | 醫學工程學研究所 |
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