Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/11416
標題: 溫度敏感性與磁性奈米顆粒之製備以及藥物傳輸系統之應用
Preparation and Application of Thermosensitive and Magnetic Nanoparticles in Drug Delivery System
作者: 連怡欣
Lien, Yi-Hsin
關鍵字: 溫度敏感性
thermosensitive
藥物傳輸系統
細胞毒性
drug delivery
cytotoxicity
出版社: 材料科學與工程學系所
引用: 1. Brandl, F.; Kastner, F.; Gschwind, R. M.; Blunk, T.; Tesmar, J.; Gopferich, A. Hydrogel-based drug delivery systems: Comparison of drug diffusivity and release kinetics,Journal of Controlled Release, 2010, 142(2), 221-228. 2. Huang, X.; Brazel, C. S. On the importance and mechanisms of burst release in matrix-controlled drug delivery systems,Journal of Controlled Release, 2001, 73(2-3), 121-136. 3. Slowing, I. I.; Vivero-Escoto, J. L.; Wu, C.-W.; Lin, V. S. Y. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers,Advanced Drug Delivery Reviews, 2008, 60(11), 1278-1288. 4. Needham, D.; Dewhirst, M. W. The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors,Adv Drug Deliv Rev, 2001, 53(3), 285-305. 5. Ozdemir, N.; Tuncel, A.; Kang, M.; Denkbas, E. B. Preparation and characterization of thermosensitive submicron particles for gene delivery,J Nanosci Nanotechnol, 2006, 6(9-10), 2804-2810. 6. Dawson, K. A.; Salvati, A.; Lynch, I. Nanotoxicology: Nanoparticles reconstruct lipids,Nat Nano, 2009, 4(2), 84-85. 7. Shen, Y.; Kuang, M.; Shen, Z.; Nieberle, J.; Duan, H.; Frey, H. Gold Nanoparticles Coated with a Thermosensitive Hyperbranched Polyelectrolyte: Towards Smart Temperature and pH Nanosensors,Angewandte Chemie International Edition, 2008, 47(12), 2227-2230. 8. Zhen, L.; Gong, Y. X.; Jiang, J. T.; Shao, W. Z. Electromagnetic properties of FeNi alloy nanoparticles prepared by hydrogen-thermal reduction method,Journal of Applied Physics, 2008, 104(3), 034312-5. 9. Yasuaki, E. Photo-switching magnetic materials,Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 2006, 7(2-3), 69-88. 10. Gyenes, T.; Torma, V.; Gyarmati, B.; Zrinyi, M. Synthesis and swelling properties of novel pH-sensitive poly(aspartic acid) gels,Acta Biomaterialia, 2008, 4(3), 733-744. 11. Zhang, J.-T.; Bhat, R.; Jandt, K. D. Temperature-sensitive PVA/PNIPAAm semi-IPN hydrogels with enhanced responsive properties,Acta Biomaterialia, 2009, 5(1), 488-497. 12. Bedard, M. F.; De Geest, B. G.; Skirtach, A. G.; Mohwald, H.; Sukhorukov, G. B. Polymeric microcapsules with light responsive properties for encapsulation and release,Advances in Colloid and Interface Science, 2010, 158(1-2), 2-14. 13. Hoffman, A. S. Applications of thermally reversible polymers and hydrogels in therapeutics and diagnostics,Journal of Controlled Release, 1987, 6(1), 297-305. 14. Kumar, A.; Srivastava, A.; Galaev, I. Y.; Mattiasson, B. Smart polymers: Physical forms and bioengineering applications,Progress in Polymer Science, 2007, 32(10), 1205-1237. 15. Dai, J.; Nagai, T.; Wang, X.; Zhang, T.; Meng, M.; Zhang, Q. pH-sensitive nanoparticles for improving the oral bioavailability of cyclosporine A,International Journal of Pharmaceutics, 2004, 280(1-2), 229-240. 16. Seow, W. Y.; Xue, J. M.; Yang, Y.-Y. Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles,Biomaterials, 2007, 28(9), 1730-1740. 17. Liu, L.; Jin, P.; Cheng, M.; Zhang, G.; Zhang, F. 5-Fluorouracil-loaded Self-assembled pH-sensitive Nanoparticles as Novel Drug Carrier for Treatment of Malignant Tumors,Chinese Journal of Chemical Engineering, 2006, 14(3), 377-382. 18. Bae, Y.; Jang, W.-D.; Nishiyama, N.; Fukushima, S.; Kataoka, K. Multifunctional polymeric micelles with folate-mediated cancer cell targeting and pH-triggered drug releasing properties for active intracellular drug delivery,Molecular BioSystems, 2005, 1(3), 242-250. 19. Bae, Y.; Fukushima, S.; Harada, A.; Kataoka, K. Design of Environment-Sensitive Supramolecular Assemblies for Intracellular Drug Delivery: Polymeric Micelles that are Responsive to Intracellular pH Change,Angewandte Chemie International Edition, 2003, 42(38), 4640-4643. 20. Bae, Y.; Nishiyama, N.; Fukushima, S.; Koyama, H.; Yasuhiro, M.; Kataoka, K. Preparation and Biological Characterization of Polymeric Micelle Drug Carriers with Intracellular pH-Triggered Drug Release Property:  Tumor Permeability, Controlled Subcellular Drug Distribution, and Enhanced in Vivo Antitumor Efficacy, Bioconjugate Chemistry, 2004, 16(1), 122-130. 21. Du, J.-Z.; Du, X.-J.; Mao, C.-Q.; Wang, J. Tailor-Made Dual pH-Sensitive Polymer–Doxorubicin Nanoparticles for Efficient Anticancer Drug Delivery,Journal of the American Chemical Society, 2011, 133(44), 17560-17563. 22. Alvarez-Lorenzo, C.; Bromberg, L.; Concheiro, A. Light-sensitive Intelligent Drug Delivery Systems,Photochemistry and Photobiology, 2009, 85(4), 848-860. 23. Pouliquen, G.; Tribet, C. Light-Triggered Association of Bovine Serum Albumin and Azobenzene-Modified Poly(acrylic acid) in Dilute and Semidilute Solutions, Macromolecules, 2005, 39(1), 373-383. 24. Gil, E. S.; Hudson, S. M. Stimuli-reponsive polymers and their bioconjugates,Progress in Polymer Science, 2004, 29(12), 1173-1222. 25. Alarcon, C. d. l. H.; Pennadam, S.; Alexander, C. Stimuli responsive polymers for biomedical applications,Chemical Society Reviews, 2005, 34(3), 276-285. 26. Escobar-Chavez, J. J.; Lopez-Cervantes, M.; Naik, A.; Kalia, Y. N.; Quintanar-Guerrero, D.; Ganem-Quintanar, A. Applications of thermoreversible pluronic F-127 gels in pharmaceutical formulations,Journal of Pharmacy and Pharmaceutical Sciences, 2006, 9(3), 339-358. 27. Gonzales, M.; Krishnan, K. M. Phase transfer of highly monodisperse iron oxide nanocrystals with Pluronic F127 for biomedical applications,Journal of Magnetism and Magnetic Materials, 2007, 311(1), 59-62. 28. 詹宗桂,鍾宜璋. 磁場誘導藥物控制釋放之載體設計,化學, 2010, 68(3), 203-213. 29. H.G, S. Poly(N-isopropylacrylamide): experiment, theory and application,Progress in Polymer Science, 1992, 17(2), 163-249. 30. Tam, K. C.; Wu, X. Y.; Pelton, R. H. Viscometry—a useful tool for studying conformational changes of poly(N-isopropylacrylamide) in solutions,Polymer, 1992, 33(2), 436-438. 31. Zhang, J. X.; Qiu, L. Y.; Jin, Y.; Zhu, K. J. Controlled nanoparticles formation by self-assembly of novel amphiphilic polyphosphazenes with poly (N-isopropylacrylamide) and ethyl glycinate as side groups,Reactive and Functional Polymers, 2006, 66(12), 1630-1640. 32. Topp, M. D. C.; Dijkstra, P. J.; Talsma, H.; Feijen, J. Thermosensitive Micelle-Forming Block Copolymers of Poly(ethylene glycol) and Poly(N-isopropylacrylamide),Macromolecules, 1997, 30(26), 8518-8520. 33. Neradovic, D.; van Nostrum, C. F.; Hennink, W. E. Thermoresponsive Polymeric Micelles with Controlled Instability Based on Hydrolytically Sensitive N-Isopropylacrylamide Copolymers,Macromolecules, 2001, 34(22), 7589-7591. 34. Neradovic, D.; Soga, O.; Van Nostrum, C. F.; Hennink, W. E. The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups,Biomaterials, 2004, 25(12), 2409-2418. 35. Nakayama, M.; Okano, T. Multi-targeting cancer chemotherapy using temperature-responsive drug carrier systems,Reactive and Functional Polymers, 2011, 71(3), 235-244. 36. Azad Malik, M.; O''Brien, P.; Revaprasadu, N. Synthesis of TOPO-capped Mn-doped ZnS and CdS quantum dots,Journal of Materials Chemistry, 2001, 11(9), 2382-2386. 37. Ono, K.; Okuda, R.; Ishii, Y.; Kamimura, S.; Oshima, M. Synthesis of Ferromagnetic Mn−Pt Nanoparticles from Organometallic Precursors,The Journal of Physical Chemistry B, 2003, 107(9), 1941-1942. 38. Garcia-Camara, B.; Saiz, J. M.; Gonzalez, F.; Moreno, F. Nanoparticles with unconventional scattering properties: Size effects,Optics Communications, 2010, 283(3), 490-496. 39. Haag, R.; Kratz, F. Polymer therapeutics: Concepts and applications,Angewandte Chemie-International Edition, 2006, 45(8), 1198-1215. 40. Gelperina, S.; Kisich, K.; Iseman, M. D.; Heifets, L. The Potential Advantages of Nanoparticle Drug Delivery Systems in Chemotherapy of Tuberculosis,Am. J. Respir. Crit. Care Med., 2005, 172(12), 1487-1490. 41. Kumari, A.; Yadav, S. K.; Yadav, S. C. Biodegradable polymeric nanoparticles based drug delivery systems,Colloids and Surfaces B: Biointerfaces, 2010, 75(1), 1-18. 42. Gupta, A. K.; Gupta, M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications,Biomaterials, 2005, 26(18), 3995-4021. 43. Schwertmann, U.; Cornell, R. M. Magnetite; Wiley-VCH Verlag GmbH, 2007,135-140. 44. Epherre, R.; Goglio, G.; Mornet, S.; Duguet, E. In Comprehensive Biomaterials; Editor-in-Chief: Paul, D., Ed.; Elsevier: Oxford, 2011, p 575-593. 45. Dave, S. R.; Gao, X. Monodisperse magnetic nanoparticles for biodetection, imaging, and drug delivery: a versatile and evolving technology,Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2009, 1(6), 583-609. 46. Cheng, F.-Y.; Su, C.-H.; Yang, Y.-S.; Yeh, C.-S.; Tsai, C.-Y.; Wu, C.-L.; Wu, M.-T.; Shieh, D.-B. Characterization of aqueous dispersions of Fe3O4 nanoparticles and their biomedical applications,Biomaterials, 2005, 26(7), 729-738. 47. El-Sheikh, S. M.; Harraz, F. A.; Abdel-Halim, K. S. Catalytic performance of nanostructured iron oxides synthesized by thermal decomposition technique,Journal of Alloys and Compounds, 2009, 487(1-2), 716-723. 48. Krishnan, K.; Pakhomov, A.; Bao, Y.; Blomqvist, P.; Chun, Y.; Gonzales, M.; Griffin, K.; Ji, X.; Roberts, B. Nanomagnetism and spin electronics: materials, microstructure and novel properties,Journal of Materials Science, 2006, 41(3), 793-815. 49. Wu, J.-H.; Ko, S. P.; Liu, H.-L.; Kim, S.; Ju, J.-S.; Kim, Y. K. Sub 5 nm magnetite nanoparticles: Synthesis, microstructure, and magnetic properties,Materials Letters, 2007, 61(14-15), 3124-3129. 50. Martinez-Mera, I.; Espinosa-Pesqueira, M. E.; Perez-Hernandez, R.; Arenas-Alatorre, J. Synthesis of magnetite (Fe3O4) nanoparticles without surfactants at room temperature,Materials Letters, 2007, 61(23-24), 4447-4451. 51. Latham, A. H.; Williams, M. E. Controlling Transport and Chemical Functionality of Magnetic Nanoparticles,Accounts of Chemical Research, 2008, 41(3), 411-420. 52. Wu, T.-M.; Yen, S.-J.; Chen, E.-C.; Sung, T.-W.; Chiang, R.-K. Conducting and magnetic behaviors of monodispersed iron oxide/polypyrrole nanocomposites synthesized by in situ chemical oxidative polymerization,Journal of Polymer Science Part A: Polymer Chemistry, 2007, 45(20), 4647-4655. 53. Lu, A. H.; Salabas, E. L.; Schuth, F. Magnetic nanoparticles: Synthesis, protection, functionalization, and application,Angewandte Chemie-International Edition, 2007, 46(8), 1222-1244. 54. 陳東煌. 複合奈米粒子有趣的人造原子,科學發展, 2006, 40840-45. 55. Berry, C. C. Progress in functionalization of magnetic nanoparticles for applications in biomedicine,Journal of Physics D-Applied Physics, 2009, 42(22), -. 56. Rana, S.; White, P.; Bradley, M. Synthesis of magnetic beads for solid phase synthesis and reaction scavenging,Tetrahedron Letters, 1999, 40(46), 8137-8140. 57. Liu, X. Q.; Guan, Y. P.; Ma, Z. Y.; Liu, H. Z. Surface modification and characterization of magnetic polymer nanospheres prepared by miniemulsion polymerization,Langmuir, 2004, 20(23), 10278-10282. 58. Kawashita, M.; Tanaka, M.; Kokubo, T.; Inoue, Y.; Yao, T.; Hamada, S.; Shinjo, T. Preparation of ferrimagnetic magnetite microspheres for in situ hyperthermic treatment of cancer,Biomaterials, 2005, 26(15), 2231-2238. 59. Yague, C.; Moros, M.; Grazu, V.; Arruebo, M.; Santamaria, J. Synthesis and stealthing study of bare and PEGylated silica micro- and nanoparticles as potential drug-delivery vectors,Chemical Engineering Journal, 2008, 137(1), 45-53. 60. Ichiyanagi, Y.; Moritake, S.; Taira, S.; Setou, M. Functional magnetic nanoparticles for medical application,Journal of Magnetism and Magnetic Materials, 2007, 310(2, Part 3), 2877-2879. 61. Liu, J.; Pelton, R.; Hrymak, A. N. Properties of poly(N-isopropylacrylamide)- grafted colloidal silica,Journal of Colloid and Interface Science, 2000, 227(2), 408-411. 62. Barnakov, Y. A.; Yu, M. H.; Rosenzweig, Z. Manipulation of the Magnetic Properties of Magnetite−Silica Nanocomposite Materials by Controlled Stober Synthesis,Langmuir, 2005, 21(16), 7524-7527. 63. Mazaleyrat, F.; Ammar, M.; LoBue, M.; Bonnet, J. P.; Audebert, P.; Wang, G. Y.; Champion, Y.; Hytch, M.; Snoeck, E. Silica coated nanoparticles: Synthesis, magnetic properties and spin structure,Journal of Alloys and Compounds, 2009, 483(1-2), 473-478. 64. Shao, L.; Caruntu, D.; Chen, J. F.; O''Connor, C. J.; Zhou, W. L. Fabrication of magnetic hollow silica nanospheres for bioapplications,Journal of Applied Physics, 2005, 97(10), 10Q908. 65. Shao, D.; Xia, A.; Hu, J.; Wang, C.; Yu, W. Monodispersed magnetite/silica composite microspheres: Preparation and application for plasmid DNA purification,Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2008, 322(1-3), 61-65. 66. Stober, W.; Fink, A.; Bohn, E. Controlled growth of monodisperse silica spheres in the micron size range,Journal of Colloid and Interface Science, 1968, 26(1), 62-69. 67. Lu, Y.; Yin, Y.; Mayers, B. T.; Xia, Y. Modifying the Surface Properties of Superparamagnetic Iron Oxide Nanoparticles through A Sol−Gel Approach,Nano Letters, 2002, 2(3), 183-186. 68. Zhang, M.; Cushing, B. L.; O''Connor, C. J. Synthesis and characterization of monodisperse ultra-thin silica-coated magnetic nanoparticles,Nanotechnology, 2008, 19(8), 085601. 69. Santra, S.; Tapec, R.; Theodoropoulou, N.; Dobson, J.; Hebard, A.; Tan, W. H. Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: The effect of nonionic surfactants,Langmuir, 2001, 17(10), 2900-2906. 70. Narita, A.; Naka, K.; Chujo, Y. Facile control of silica shell layer thickness on hydrophilic iron oxide nanoparticles via reverse micelle method,Colloids and Surfaces a-Physicochemical and Engineering Aspects, 2009, 336(1-3), 46-56. 71. Yi, D. K.; Lee, S. S.; Papaefthymiou, G. C.; Ying, J. Y. Nanoparticle architectures templated by SiO2/Fe2O3 nanocomposites,Chemistry of Materials, 2006, 18(3), 614-619. 72. Jain, T. K.; Reddy, M. K.; Morales, M. A.; Leslie-Pelecky, D. L.; Labhasetwar, V. Biodistribution, Clearance, and Biocompatibility of Iron Oxide Magnetic Nanoparticles in Rats,Molecular Pharmaceutics, 2008, 5(2), 316-327. 73. Hu, S.-H.; Liu, T.-Y.; Liu, D.-M.; Chen, S.-Y. Nano-ferrosponges for controlled drug release,Journal of Controlled Release, 2007, 121(3), 181-189. 74. Rahimi, M.; Yousef, M.; Cheng, Y.; Meletis, E. I.; Eberhart, R. C.; Nguyen, K. Formulation and characterization of a covalently coated magnetic nanogel,J Nanosci Nanotechnol, 2009, 9(7), 4128-4134. 75. Shamim, N.; Hong, L.; Hidajat, K.; Uddin, M. S. Thermosensitive polymer (N-isopropylacrylamide) coated nanomagnetic particles: Preparation and characterization,Colloids and Surfaces B-Biointerfaces, 2007, 55(1), 51-58. 76. Shamim, N.; Hong, L.; Hidajat, K.; Uddin, M. S. Thermosensitive-polymer-coated magnetic nanoparticles: Adsorption and desorption of Bovine Serum Albumin,Journal of Colloid and Interface Science, 2006, 304(1), 1-8. 77. Shamim, N.; Hong, L.; Hidajat, K.; Uddin, M. S. Thermosensitive polymer coated nanomagnetic particles for separation of bio-molecules,Separation and Purification Technology, 2007, 53(2), 164-170. 78. Rades, Y. P. a. T. Pharmaceutics - Drug Delivery and Targeting; Royal Pharmaceutical Society of Great Britain, 2009. 79. Irvine, D. J. Drug delivery: One nanoparticle, one kill,Nat Mater, 2011, 10(5), 342-343. 80. Poon, Z.; Chen, S.; Engler, A. C.; Lee, H.-i.; Atas, E.; von Maltzahn, G.; Bhatia, S. N.; Hammond, P. T. Ligand-Clustered “Patchy” Nanoparticles for Modulated Cellular Uptake and In Vivo Tumor Targeting,Angewandte Chemie International Edition, 2010, 49(40), 7266-7270. 81. Ho, K.; Lapitsky, Y.; Shi, M.; Shoichet, M. S. Tunable immunonanoparticle binding to cancer cells: thermodynamic analysis of targeted drug delivery vehicles,Soft Matter, 2009, 5(5), 1074-1080. 82. Hua, M.-Y.; Yang, H.-W.; Chuang, C.-K.; Tsai, R.-Y.; Chen, W.-J.; Chuang, K.-L.; Chang, Y.-H.; Chuang, H.-C.; Pang, S.-T. Magnetic-nanoparticle-modified paclitaxel for targeted therapy for prostate cancer,Biomaterials, 2010, 31(28), 7355-7363. 83. Hua, M.-Y.; Yang, H.-W.; Liu, H.-L.; Tsai, R.-Y.; Pang, S.-T.; Chuang, K.-L.; Chang, Y.-S.; Hwang, T.-L.; Chang, Y.-H.; Chuang, H.-C.; Chuang, C.-K. Superhigh-magnetization nanocarrier as a doxorubicin delivery platform for magnetic targeting therapy,Biomaterials, 2011, 32(34), 8999-9010. 84. Wei, H.; Zhang, X.-Z.; Zhou, Y.; Cheng, S.-X.; Zhuo, R.-X. Self-assembled thermoresponsive micelles of poly(N-isopropylacrylamide-b-methylmethacrylate), Biomaterials, 2006, 27(9), 2028-2034. 85. Zhang, L.; Guo, R.; Yang, M.; Jiang, X.; Liu, B. Thermo and pH Dual-Responsive Nanoparticles for Anti-Cancer Drug Delivery,Advanced Materials, 2007, 19(19), 2988-2992. 86. Zhu, S.; Zhou, Z.; Zhang, D. Control of Drug Release through the In Situ Assembly of Stimuli-Responsive Ordered Mesoporous Silica with Magnetic Particles, ChemPhysChem, 2007, 8(17), 2478-2483. 87. Tian, B.-S.; Yang, C. Temperature-Responsive Nanocomposites Based on Mesoporous SBA-15 Silica and PNIPAAm: Synthesis and Characterization,The Journal of Physical Chemistry C, 2009, 113(12), 4925-4931. 88. Zhu, S.; Zhou, Z.; Zhang, D.; Jin, C.; Li, Z. Design and synthesis of delivery system based on SBA-15 with magnetic particles formed in situ and thermo-sensitive PNIPA as controlled switch,Microporous and Mesoporous Materials, 2007, 106(1-3), 56-61. 89. Zhu, Y. F.; Kaskel, S.; Ikoma, T.; Hanagata, N. Magnetic SBA-15/poly(N-isopropylacrylamide) composite: Preparation, characterization and temperature-responsive drug release property,Microporous and Mesoporous Materials, 2009, 123(1-3), 107-112. 90. You, Y.-Z.; Kalebaila, K. K.; Brock, S. L.; Oupicky, D. Temperature-Controlled Uptake and Release in PNIPAM-Modified Porous Silica Nanoparticles,Chemistry of Materials, 2008, 20(10), 3354-3359. 91. Andreza de Sousa, K. C. d. S., Nelcy D. S. Mohallem, Ricardo Geraldo de Sousa and Edesia Martins Barros de Sousa. Multifunctional Nanocomposites Based on Mesoporous Silica: Potential Applications in Biomedicine, Advances in Diverse Industrial Applications of Nanocomposites; InTech, 2011. 92. Kreyling, W. G.; Hirn, S.; Schleh, C. Nanoparticles in the lung,Nat Biotech, 2010, 28(12), 1275-1276. 93. Semmler-Behnke, M.; Kreyling, W. G.; Lipka, J.; Fertsch, S.; Wenk, A.; Takenaka, S.; Schmid, G.; Brandau, W. Biodistribution of 1.4- and 18-nm Gold Particles in Rats,Small, 2008, 4(12), 2108-2111. 94. Colvin, V. L. The potential environmental impact of engineered nanomaterials,Nat Biotech, 2003, 21(10), 1166-1170. 95. Borm, P. J. A. Particle toxicology: from coal mining to nanotechnology, Inhalation Toxicology, 2002, 14(3), 311-324. 96. Balasubramanian, S. K.; Jittiwat, J.; Manikandan, J.; Ong, C.-N.; Yu, L. E.; Ong, W.-Y. Biodistribution of gold nanoparticles and gene expression changes in the liver and spleen after intravenous administration in rats,Biomaterials, 2010, 31(8), 2034-2042. 97. Choi, H. S.; Ipe, B. I.; Misra, P.; Lee, J. H.; Bawendi, M. G.; Frangioni, J. V. Tissue- and Organ-Selective Biodistribution of NIR Fluorescent Quantum Dots,Nano Letters, 2009, 9(6), 2354-2359. 98. Liu, D.; Mori, A.; Huang, L. Role of liposome size and RES blockade in controlling biodistribution and tumor uptake of GM1-containing liposomes,Biochimica et Biophysica Acta (BBA) - Biomembranes, 1992, 1104(1), 95-101. 99. He, Q.; Zhang, Z.; Gao, F.; Li, Y.; Shi, J. In vivo Biodistribution and Urinary Excretion of Mesoporous Silica Nanoparticles: Effects of Particle Size and PEGylation,Small, 2011, 7(2), 271-280. 100. Sonavane, G.; Tomoda, K.; Makino, K. Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size,Colloids and Surfaces B-Biointerfaces, 2008, 66(2), 274-280. 101. Chen, M.; von Mikecz, A. Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles,Experimental Cell Research, 2005, 305(1), 51-62. 102. Nishimori, H.; Kondoh, M.; Isoda, K.; Tsunoda, S.-i.; Tsutsumi, Y.; Yagi, K. Silica nanoparticles as hepatotoxicants,European Journal of Pharmaceutics and Biopharmaceutics, 2009, 72(3), 496-501. 103. Olmedo, D.; Guglielmotti, M. B.; Cabrini, R. L. An experimental study of the dissemination of Titanium and Zirconium in the body,Journal of Materials Science: Materials in Medicine, 2002, 13(8), 793-796. 104. Ye, Y.; Liu, J.; Chen, M.; Sun, L.; Lan, M. In vitro toxicity of silica nanoparticles in myocardial cells,Environmental Toxicology and Pharmacology, 2010, 29(2), 131-137. 105. Ye, Y.; Liu, J.; Xu, J.; Sun, L.; Chen, M.; Lan, M. Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line,Toxicology in Vitro, 2010, 24(3), 751-758. 106. Nel, A.; Xia, T.; Madler, L.; Li, N. Toxic potential of materials at the nanolevel,Science, 2006, 311(5761), 622-627. 107. Lu X, Q. J., Zhou H, Gan Q, Tang W, Lu J, Yuan Y, Liu C In vitro cytotoxicity and induction of apoptosis by silica nanoparticles in human HepG2 hepatoma cells,International Journal of Nanomedicine, 2011, 6(1), 1889-1901. 108. Roiter, Y.; Ornatska, M.; Rammohan, A. R.; Balakrishnan, J.; Heine, D. R.; Minko, S. Interaction of nanoparticles with lipid membrane,Nano Letters, 2008, 8(3), 941-944. 109. Wang, F.; Jiao, C.; Liu, J.; Yuan, H.; Lan, M.; Gao, F. Oxidative mechanisms contribute to nanosize silican dioxide-induced developmental neurotoxicity in PC12 cells,Toxicology in Vitro, 2011, 25(8), 1548-1556. 110. Sun, L.; Li, Y.; Liu, X.; Jin, M.; Zhang, L.; Du, Z.; Guo, C.; Huang, P.; Sun, Z. Cytotoxicity and mitochondrial damage caused by silica nanoparticles,Toxicology in Vitro, 2011, 25(8), 1619-1629. 111. Vihola, H.; Laukkanen, A.; Valtola, L.; Tenhu, H.; Hirvonen, J. Cytotoxicity of thermosensitive polymers poly(N-isopropylacrylamide), poly(N-vinylcaprolactam) and amphiphilically modified poly(N-vinylcaprolactam),Biomaterials, 2005, 26(16), 3055-3064. 112. Hinrichs, W. L. J.; Schuurmans-Nieuwenbroek, N. M. E.; van de Wetering, P.; Hennink, W. E. Thermosensitive polymers as carriers for DNA delivery,Journal of Controlled Release, 1999, 60(2-3), 249-259. 113. Turk, M.; Dincer, S.; Yuluğ, I. G.; Pişkin, E. In vitro transfection of HeLa cells with temperature sensitive polycationic copolymers,Journal of Controlled Release, 2004, 96(2), 325-340. 114. Tanii, H.; Hashimoto, K. Neurotoxicity of acrylamide and related compounds in rats,Archives of Toxicology, 1983, 54(3), 203-213. 115. Wadajkar, A. S.; Koppolu, B.; Rahimi, M.; Nguyen, K. T. Cytotoxic evaluation of N-isopropylacrylamide monomers and temperature-sensitive poly(N- isopropylacrylamide) nanoparticles,Journal of Nanoparticle Research, 2009, 11(6), 1375-1382. 116. Rahimi, M.; Wadajkar, A.; Subramanian, K.; Yousef, M.; Cui, W. N.; Hsieh, J. T.; Nguyen, K. T. In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery,Nanomedicine-Nanotechnology Biology and Medicine, 2010, 6(5), 672-680. 117. Naha, P. C.; Bhattacharya, K.; Tenuta, T.; Dawson, K. A.; Lynch, I.; Gracia, A.; Lyng, F. M.; Byrne, H. J. Intracellular localisation, geno- and cytotoxic response of polyN-isopropylacrylamide (PNIPAM) nanoparticles to human keratinocyte (HaCaT) and colon cells (SW 480),Toxicology Letters, 2010, 198(2), 134-143. 118. Huo, D.; Li, Y.; Qian, Q.; Kobayashi, T. Temperature-pH sensitivity of bovine serum albumin protein-microgels based on cross-linked poly(N-isopropylacrylamide- co-acrylic acid),Colloids and Surfaces B: Biointerfaces, 2006, 50(1), 36-42. 119. Duracher, D.; Veyret, R.; Elaissari, A.; Pichot, C. Adsorption of bovine serum albumin protein onto amino-containing thermosensitive core-shell latexes,Polymer International, 2004, 53(5), 618-626. 120. Nguyen, T. L. U.; Farrugia, B.; Davis, T. P.; Barner-Kowollik, C.; Stenzel, M. H. Core-shell microspheres with surface grafted poly(vinyl alcohol) as drug carriers for the treatment of hepatocellular carcinoma,Journal of Polymer Science Part a-Polymer Chemistry, 2007, 45(15), 3256-3272. 121. 日本組織培養學會, 辛., 上野洋一郎. 組織培養技術; 藝軒: 台北市, 民76. 122. Ma, M.; Wu, Y.; Zhou, J.; Sun, Y.; Zhang, Y.; Gu, N. Size dependence of specific power absorption of Fe3O4 particles in AC magnetic field,Journal of Magnetism and Magnetic Materials, 2004, 268(1-2), 33-39. 123. Atsumi, T.; Jeyadevan, B.; Sato, Y.; Tohji, K. Heating efficiency of magnetite particles exposed to AC magnetic field,Journal of Magnetism and Magnetic Materials, 2007, 310(2, Part 3), 2841-2843. 124. Kohler, N.; Sun, C.; Wang, J.; Zhang, M. Q. Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells,Langmuir, 2005, 21(19), 8858-8864. 125. Ishida, N.; Kobayashi, M. Interaction forces measured between poly(N-isopropylacrylamide) grafted surface and hydrophobic particle,Journal of Colloid and Interface Science, 2006, 297(2), 513-519. 126. Deng, Y. H.; Yang, W. L.; Wang, C. C.; Fu, S. K. A Novel Approach for Preparation of Thermoresponsive Polymer Magnetic Microspheres with Core–Shell Structure, Advanced Materials, 2003, 15(20), 1729-1732. 127. Zhang, J.; Misra, R. D. K. Magnetic drug-targeting carrier encapsulated with thermosensitive smart polymer: Core-shell nanoparticle carrier and drug release response,Acta Biomaterialia, 2007, 3(6), 838-850. 128. Davazoglou, D.; Vamvakas, V. E. Optical dispersion analysis within the IR range of thermally grown and TEOS deposited SiO2 films,Microelectronics Reliability, 1999, 39(2), 285-289. 129. Plinio, I. Infrared spectroscopy of sol–gel derived silica-based films: a spectra-microstructure overview,Journal of Non-Crystalline Solids, 2003, 316(2-3), 309-319. 130. Yilmaz, E.; Bengisu, M. Drug entrapment in silica microspheres through a single step sol–gel process and in vitro release behavior,Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2006, 77B(1), 149-155. 131. Li, L.; Yang, X.; Liu, F.; Shang, J.; Yan, G.; Li, W. Thermosensitive poly(N-isopropylacrylamide)-b-polycaprolactone-b-poly(N-isopropylacrylamide) triblock copolymers prepared via atom transfer radical polymerization for control of cell adhesion and detachment Journal of the Chilean Chemical Society, 2009, 54397-400. 132. Tsukagoshi, T.; Kondo, Y.; Yoshino, N. Preparation of thin polymer films with drug release and protein adsorption resistance,Colloids and Surfaces B: Biointerfaces, 2007, 55(1), 19-25. 133. Seino, M.; Yokomachi, K.; Hayakawa, T.; Kikuchi, R.; Kakimoto, M.-a.; Horiuchi, S. Preparation of poly(N-isopropylacrylamide) grafted silica bead using hyperbranched polysiloxysilane as polymer brush and application to temperature-responsive HPLC,Polymer, 2006, 47(6), 1946-1952. 134. Suzuki, K.; Yumura, T.; Tanaka, Y.; Akashi, M. Thermo-responsive release from interpenetrating porous silica–poly(N-isopropylacrylamide) hybrid gels,Journal of Controlled Release, 2001, 75(1–2), 183-189. 135. Chambon, P.; Chen, L.; Furzeland, S.; Atkins, D.; Weaver, J. V. M.; Adams, D. J. Poly(N-isopropylacrylamide) branched polymer nanoparticles,Polymer Chemistry, 2011, 2(4), 941-949. 136. Wu, T.; Zhang, Y.; Wang, X.; Liu, S. Fabrication of Hybrid Silica Nanoparticles Densely Grafted with Thermoresponsive Poly(N-isopropylacrylamide) Brushes of Controlled Thickness via Surface-Initiated Atom Transfer Radical Polymerization,Chemistry of Materials, 2007, 20(1), 101-109. 137. Chen, S.-b.; Zhong, H.; Zhang, L.-l.; Wang, Y.-f.; Cheng, Z.-p.; Zhu, Y.-l.; Yao, C. Synthesis and characterization of thermoresponsive and biocompatible core–shell microgels based on N-isopropylacrylamide and carboxymethyl chitosan,Carbohydrate Polymers, 2010, 82(3), 747-752. 138. Tagit, O.; Janczewski, D.; Tomczak, N.; Han, M. Y.; Herek, J. L.; Vancso, G. J. Nanostructured thermoresponsive quantum dot/PNIPAM assemblies,European Polymer Journal, 2010, 46(7), 1397-1403. 139. Guo, J.; Yang, W. L.; Wang, C. C.; He, J.; Chen, J. Y. Poly(N- isopropylacrylamide)-coated luminescent/magnetic silica microspheres: Preparation, characterization, and biomedical applications,Chemistry of Materials, 2006, 18(23), 5554-5562. 140. Dey, N. S.; Majumadar, S.; Rao, M. E. B. Multiparticulate Drug Delivery Systems for Controlled Release,Tropical Journal of Pharmaceutical Research, 2008, 7(3), 1067-1075. 141. Avi, S. In Advances in Agronomy; Academic Press, 2001, p 1-49. 142. Siepmann, J.; Lecomte, F.; Bodmeier, R. Diffusion-controlled drug delivery systems: calculation of the required composition to achieve desired release profiles,Journal of Controlled Release, 1999, 60(2–3), 379-389. 143. Bajpai, A. K.; Shukla, S. K.; Bhanu, S.; Kankane, S. Responsive polymers in controlled drug delivery,Progress in Polymer Science, 2008, 33(11), 1088-1118. 144. Yuan, Q.; Venkatasubramanian, R.; Hein, S.; Misra, R. D. K. A stimulus-responsive magnetic nanoparticle drug carrier: Magnetite encapsulated by chitosan-grafted- copolymer,Acta Biomaterialia, 2008, 4(4), 1024-1037. 145. Wei, H.; Cheng, S.-X.; Zhang, X.-Z.; Zhuo, R.-X. Thermo-sensitive polymeric micelles based on poly(N-isopropylacrylamide) as drug carriers,Progress in Polymer Science, 2009, 34(9), 893-910. 146. Arıca, M. Y.; Oktem, H. A.; Oktem, Z.; Tuncel, S. A. Immobilization of catalase in poly(isopropylacrylamide-co-hydroxyethylmethacrylate) thermally reversible hydrogels,Polymer International, 1999, 48(9), 879-884. 147. Shirasaki, Y.; Tanaka, J.; Makazu, H.; Tashiro, K.; Shoji, S.; Tsukita, S.; Funatsu, T. On-Chip Cell Sorting System Using Laser-Induced Heating of a Thermoreversible Gelation Polymer to Control Flow,Analytical Chemistry, 2005, 78(3), 695-701. 148. Wei, H.; Zhang, X.-Z.; Chen, W.-Q.; Cheng, S.-X.; Zhuo, R.-X. Self-assembled thermosensitive micelles based on poly(L-lactide-star block-N-isopropylacrylamide) for drug delivery,Journal of Biomedical Materials Research Part A, 2007, 83A(4), 980-989. 149. Wei, H.; Zhang, X.-Z.; Cheng, H.; Chen, W.-Q.; Cheng, S.-X.; Zhuo, R.-X. Self-assembled thermo- and pH responsive micelles of poly(10-undecenoic acid-b-N-isopropylacrylamide) for drug delivery,Journal of Controlled Release, 2006, 116(3), 266-274. 150. Ding, X. B.; Sun, Z. H.; Zhang, W. C.; Peng, Y. X.; Wan, G. X.; Jiang, Y. Y. Adsorption/desorption of protein on magnetic particles covered by thermosensitive polymers,Journal of Applied Polymer Science, 2000, 77(13), 2915-2920. 151. Elaissari, A.; Bourrel, V. Thermosensitive magnetic latex particles for controlling protein adsorption and desorption,Journal of Magnetism and Magnetic Materials, 2001, 225(1–2), 151-155. 152. Kim, J. U.; O''Shaughnessy, B. Morphology selection of nanoparticle dispersions by polymer media,Physical Review Letters, 2002, 89(23), 238301-4. 153. Luzinov, I.; Minko, S.; Tsukruk, V. V. Responsive brush layers: from tailored gradients to reversibly assembled nanoparticles,Soft Matter, 2008, 4(4), 714-725. 154. Zhang, X. Z.; Zhuo, R. X.; Cui, J. Z.; Zhang, J. T. A novel thermo-responsive drug delivery system with positive controlled release,International Journal of Pharmaceutics, 2002, 235(1-2), 43-50. 155. Lien, Y. H.; Wu, T. M. Preparation and characterization of thermosensitive polymers grafted onto silica-coated iron oxide nanoparticles,Journal of Colloid and Interface Science, 2008, 326(2), 517-521. 156. Ge, S. R.; Kojio, K.; Takahara, A.; Kajiyama, T. Bovine serum albumin adsorption onto immobilized organotrichlorosilane surface: Influence of the phase separation on protein adsorption patterns,Journal of Biomaterials Science-Polymer Edition, 1998, 9(2), 131-150. 157. Matsukata, M.; Nishino, M.; Ping Gong, J.; Osada, Y.; Sakurai, Y.; Okano, T. Adsorption of bovine serum albumin to yeast protoplast,Colloids and Surfaces B: Biointerfaces, 1999, 13(4), 203-211. 158. Kawaguchi, H.; Kawahara, M.; Yaguchi, N.; Hoshino, F.; Ohtsuka, Y. Hydrogel microspheres.1. prepareation of monodisperse hydrogel microspheres of sub-micron or micron size,Polymer Journal, 1988, 20(10), 903-909. 159. Stenzel, M. H.; Nguyen, T. L. U.; Farrugia, B.; Davis, T. P.; Barner-Kowollik, C. Core-shell microspheres with surface grafted poly(vinyl alcohol) as drug carriers for the treatment of hepatocellular carcinoma,Journal of Polymer Science Part a-Polymer Chemistry, 2007, 45(15), 3256-3272. 160. Stenzel, M. H.; Nguyen, T. L. U.; Tey, S. Y.; Pourgholami, M. H.; Morris, D. L.; Davis, T. P.; Barner-Kowollik, C. Synthesis of semi-biodegradable crosslinked microspheres for the delivery of 1,25 dihydroxyvitamin D-3 for the treatment of hepatocellular carcinoma,European Polymer Journal, 2007, 43(5), 1754-1767. 161. Finlay, I. F.; Stewart, G. S.; Shirley, P. S.; Woolfe, S. W.; Pourgholam
摘要: 本研究中,利用反微乳化聚合法將二氧化矽披覆在單分散6 nm氧化鐵顆粒表面,藉由反應時間與二氧化矽前驅物之濃度調控複合顆粒尺寸,再將以自由基聚合法合成的聚異丙基丙醯胺[poly(N-isopropylacrylamide), (PNIPAM)]共聚高分子接枝在此複合顆粒表面,即可製備出同時具有溫度敏感性以及磁性的奈米顆粒且結構為典型之核/殼結構。 NIPAM的低臨界轉換溫度(lower critical solution temperature,LCST)約為32°C,在與3-(甲基丙烯酰氧)丙基三甲氧基矽烷[3- (trimethoxysily) propyl methacrylate,MPS]形成共聚物接枝在複合顆粒表面後,PNIPAM共聚物所測得低臨界溶液溫度(lower critical solution temperature,LCST) 上升至35-40°C區間。此外,從動態光散射分析儀(dynamic light scattering,DLS)可觀察到粒徑會隨著溫度的升高逐漸減小,並在35-40°C會有明顯的變化。因此,所製備出的PNIPAM接枝SiO2/Fe3O4奈米顆粒具有接近人體體溫之LCST。包覆氧化鐵的目的,是使奈米顆粒帶有磁性,希望藉由外加磁場的控制,將顆粒引導至癌細胞或是特定細胞的鄰近區域,再將藥物有效控制釋放,尺寸為6 nm的氧化鐵顆粒具有超順磁的特性,表面經過二氧化矽層的披覆,經由超導量子干涉磁量儀(Superconducting Quantum Interference Device,SQUID)的測量,可以發現飽和磁化量的下降,但複合顆粒仍呈現原本的超順磁特性;並且表面接枝PNIPAM後,仍保有超順磁的特性,且不受溫度變化的影響。 將所製備出的PNIPAM接枝SiO2/Fe3O4奈米顆粒與牛血清蛋白(Bovine Serum Albumin,BSA)和維生素D3(vitamin D3)作為兩種模擬藥物,進行藥物承載與釋放試驗,使用UV可見光光譜儀(UV/VIS Spectophotometer,UV)計算所得之結果發現,藥物承載與釋放會受到溫度的影響而有所改變。BSA為水溶性之藥物,但屬於大分子,承載與釋放主要受到與PNIPAM接枝SiO2/Fe3O4奈米顆粒之間的疏水作用力影響。因此,BSA在高於PNIPAM之LCST的溫度,由於披覆在奈米顆粒表面的PNIPAM鏈段會產生糾結形成疏水性的表面,此時可利用疏水作用力與BSA鍵結,將其吸附在表面,反之,在低於LCST的溫度,PNIPAM分子鏈段伸展親水,因而無法吸附BSA。Vitamin D3承載機制表現不同,在高溫的承載量少於低溫的承載量,然而在釋放時,低溫承載的釋放量卻優於高溫承載的釋放量,表示其承載與釋放仍會受到表面PNIAPM鏈段溫度敏感性的影響。從此結果可得知,利用低溫承載較多的vitamin D3,進入人體的環境中,可幫助其釋放,以提昇治療的效果。 細胞實驗主要分為兩部份,第一部分主要探討PNIPAM接枝SiO2/ Fe3O4奈米顆粒的生物相容性,並探討其對細胞的安全性。本部份主要使用兩種細胞,哺乳動物中國倉鼠卵巢細胞(Chinese hamster ovary cell,CHO-K1),以及人類肝癌細胞(Human hepatocellular liver carcinoma,HepG2),經由溴化噻唑蓝四氮唑藍分析(3-(4,5-cimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide,MTT)、錐藍排除分析法(trypan blue)和乳酸去氫酶(Lactate dehydrogenase,LDH)的細胞存活率測試,顯示奈米顆粒呈現良好的生物相容性。並使用光學顯微鏡(Optical Microscopy,OM)觀察顆粒的添加並不會對細胞形態產生影響,也進一步使用TEM確認奈米顆粒進入細胞,並存在於細胞質的位置。第二部份主要探討承載具有活性vitamin D3 (1,25-dihydroxyvitamin D3,1,25(OH)2D3)的PNIPAM接枝SiO2/Fe3O4奈米顆粒是否有效將藥物釋放抑制癌細胞的生長。承載藥物的奈米顆粒,在短時間內從MTT並無觀察到變化,直至5天的培養,細胞存活率顯示為明顯的下降,並從LDH的觀察到細胞傷害的表現。進一步由穿透式電子顯微鏡(Transmission Electron Microscopy,TEM)觀察細胞的形態的變化,可以在第一天即發現承載藥物的奈米顆粒進入細胞,並存在於細胞質間,但還未對細胞造成傷害,將時間培養至第五天時,細胞型態明顯改變,呈現細胞傷害死亡的結果。可知,PNIPAM接枝SiO2/Fe3O4奈米顆粒具備當作藥物載體的潛力,適合應用在藥物傳輸系統上。
In this study, the multi-functional nanoparticles containing thermosensitive polymers grafted onto the surfaces of the 6-nm monodispersed Fe3O4 magnetic nanoparticles coated by silica were synthesized using reverse microemulsions. The magnetic properties of SiO2/Fe3O4 nanoparticles show superparamagnetic behavior. Thermosensitive PNIPAM [poly(N-isopropylacrylamide)] was then grafted onto the surfaces of SiO2/Fe3O4 nanoparticles, generating thermosensitive and magnetic properties of nanocomposites. The sizes of fabricated nanoparticles with core-shell structure are controlled at about 20 nm and each nanoparticle contains only one monodispersed Fe3O4 core. For thermosensibility analysis, the phase transition temperatures of multi-functional nanoparticles measured using differential scanning calorimetry (DSC) and dynamic light scanning (DLS) were at around 35~40�C. The magnetic characteristics of these multi-functional nanoparticles were also superparamagnetic. The loading and release of Bovine serum albumin (BSA) and vitamin D3 were also discussed. The main driving force to adsorb BSA is hydrophobic interaction between nanoparticles and BSA. Thus, at 50�C and 37�C, the polymeric shell presented as hydrophobic chains and could adsorb BSA; in contrast, the nanoparticles have no significant absorption at 25�C. Vitamin D3 loading and release behavior were also found to be dependent on the lower critical solution temperature (LCST) of the PNIPAM/SiO2/Fe3O4 nanoparticles. However, it is different to adsorption of BSA. These results show the loading vitamin D3 increases with increasing time and reaches a plateau over the 24 hours study at 25 and 37�C. At 37�C, the lower loading amount of vitamin D3 ~19.3 wt% is observed; while higher loading amount ~37.7 wt% is reached at 25�C, which is below the LCST of nanoparticles. In vitro drug release, drug squeezed out from the nanoparticles was observed when loading drug at 25�C and releasing at 37�C; nevertheless, the drug release system will undergo at physiological temperature so that loading temperature is better under the LCST. Cytotoxicity studies were apart from two parts. The first part was conducted on Chinese hamster ovary (CHO-K1) cells and liver cancer cells (HepG2) using 3-(4,5-cimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assays revealed that cell viability of 1 mg/mL PNIPAM grafted on SiO2/Fe3O4 nanoparticles was slightly decreased after 24h incubation as compared to the lower concentration of nanoparticles. Furthermore, the concentration of 0.5 mg/mL PNIPAM grafted on SiO2/Fe3O4 nanoparticles was totally biocompatible for 48h; however, had low cytotoxicity after 72h incubation. These PNIPAM grafted on SiO2/Fe3O4 nanoparticles did not induce the morphological change in their cellularity after the exposure for 24 and 108h. The second part was observed the effect of 1,25(OH)2D3 loading of PNIPAM grafted on SiO2/Fe3O4 nanoparticles incubated with HepG2 cells. After 5 days incubation of HepG2 liver cancer cells with 1,25(OH)2D3 loading of PNIPAM grafted on SiO2/Fe3O4 nanoparticles, cell viability significant decreased that discernible from MTT and lactate dehydrogenase (LDH) assays, which is further supported by the TEM images. In conclusion, the current study demonstrated a PNIPAM grafted on SiO2/Fe3O4 nanoparticles may be used as a potential drug delivery system for controlled release.
URI: http://hdl.handle.net/11455/11416
其他識別: U0005-0407201210430800
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-0407201210430800
Appears in Collections:材料科學與工程學系

文件中的檔案:

取得全文請前往華藝線上圖書館



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.