功能性磁性聚合物微球的制备、表征及其初步应用
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摘要
随着生物医学和生物工程相关领域研究的发展,功能性聚合物微球的制备越来越来受到人们的关注,探索聚合物微球的功能化、智能化以及将这些微球应用于药物释放、生物大分子分离、生物传感和固定化酶等方面是聚合物微球一个重要研究的方向。在这种研究背景下,本文的研究工作主要围绕着功能性磁性聚合物的制备、表征以及初步应用展开,具体涉及四氧化三铁磁性纳米粒子(Fe_3O_4)的制备及其表面改性、核—壳结构的磁性二氧化硅粒子(Fe_3O_4@SiO_2)的制备,磁场和温度双重敏感的聚合物微球(Fe_3O_4@SiO_2/PNIPAM)的制备及其用于药物载体的研究,最后,为了赋予Fe_3O_4@SiO_2/PNIPAM微球更多的功能,我们还制备荧光标记的Fe_3O_4@SiO_2/PNIPAM微球,从而获得一种整合了磁性微球、荧光微球和温敏性微球的多功能微球。具体来说,取得以下几方面的结果:
(1) 采用化学共沉淀法制备了超顺磁性的四氧化三铁纳米粒子的制备条件和工艺。
研究了影响化学共沉淀法制备四氧化三铁纳米粒子的各种因素,发现铁盐浓度、沉淀剂浓度以及沉淀剂与铁盐比例和反应温度均影响产物的性能。
最后通过采用分步升温加热的化学共沉淀法,制备了粒径大约15nm具有超顺磁性的四氧化三铁纳米粒子。
利用振动样品磁场计、X—射线衍射、透射电镜、红外等对产物进行了表征,证实了我们制备超顺磁性的四氧化三铁纳米粒子的方法的可靠性。
(2) 使用多元酸盐(柠檬酸三钠)成功地对四氧化三铁纳米粒子进行了表面改性,制备了电荷稳定的磁流体。研究了柠檬酸钠浓度对四氧化三铁纳米粒子改性效果的影响,发现在一定范围内加大柠檬酸钠用量可以使四氧化三铁纳米粒子分散稳定性逐渐增强。
利用改进的Stober法制备了不同形态的magnetite@silica复合粒子,发现通过调节柠檬酸钠对四氧化三铁纳米粒子的改性程度、控制前驱体TEOS的用量等可以控制magnetite@silica复合粒子的形态和粒径。使用TEM,DLS和SEM
Now with the research development in field of biomedicine and bioengineering, people are exploring various functional polymer microspheres which can serve as smart or intelligent tools for drug delivery, biomacromolecules purification, biosensor and enzyme immobilization,etc. Based on the research background and the development trend of polymer microspheres,the research interest of this work focused in the preparation and primary application of functionalized magnetic polymer microspheres, which involves in five parts, i.e. the preparation and surface modification of magnetite nanoparticles, preparation of magnetite@silica particles, preparation and primary application of dual-responsive polymer microspheres which possess magnetically responsive and thermoresponsive properties, and preparation of fluorescence labeled dual-responsive polymer microspheres. The results of each part are listed as follows:(1) Magnetite nanoparticles were prepared by chemical co-precipitation process. Different reaction parameters including reactant concentrate, reactant molar ratio and reaction temperature were found to dramatically influence the properties (particle size, superparamagnetic property, etc). Finally, superparamagnetic magnetite nanoparticles of about 15nm were obtained by using proper reactant concentrate, feeding ratios and controlling the reaction temperature increased stepwisely. The characterization results of vibrating sample magnetometer, X-ray diffraction and transmission electron microscope confirmed superparamagnetic magnetite particles with an average size of about 15nm were prepared.(2) By treating as-prepared magnetite nanoparticles with trisodium citrate aqueous solution, stable magnetic fluid (dispersion of magnetite nanoparticles in water) was prepared. It was found that, to some extent, more amount of trisodium citrate was used to modify the magnetite nanoparticles, more stable magnetic fluid was produced. Using the modified magnetite nanoparticles as seeds, silica-coated
magnetite particles (magnetite@silica) were prepared via a modified Stober method. It was found that the morphology of resulted magnet ite@si lie a particles is related with the extent of modification of magnetite. When magnetite particles modified with small amount of trisodium citrate were used as seeds, the magnetite@silica particles were silica-coated magnetite clusters, and when magnetite particles modified with larger amount of trisodium citrate were used as seeds, magnetite@silica shows a typical spherical shape and core-shell structure. The size of magnetite@silica particles is dependent of the amount of the precursor(tetraethyl orthosilicate).(3) Using magnetite@silica particle as seed, a dual-responsive polymer microsphere with core-shell structure was prepared by precipitation polymerization. The prepared microsphere consists of magnetite@silica core and crosslinked PNIPAM shell. The core of these microspheres could be tuned by using magnetite@silica particles of different size as seeds, and the crosslinking densities of the PNIPAM shell could be changed by changing the amount of crosslinker in the preparation recipes.The characterization results show that the prepared microspheres possesss magnetic property and thermoresponsive property, and the LCST of the microspheres could be tuned by changing the crosslinking density, when the crosslinking density of PNIPAM shell attained 25%,the LCST of the microsphere increased to 37°C. TEM and SEM observation shows that the size of the microspheres is in range of submicron scale. It is worthy noting that the method used in this study could be extended to prepare other inorganic-core-organic-shell polymer composite microspheres when various inorganic nanoparticles (Au, CdS, nanozeolite, etc.) are used, furthermore, other polymer could also be form on the surface of these inorganic particles through radical polymerization of corresponding monomers.(4)By using the prepared dual-responsive microspheres of different crosslinking densities(15%, 20% and 25%) as carrier of an anti-tumor drug (DOX), it was found that microspheres of higher cosslinking density possess lower drug loading capacity. Increasing the weight ratio between drug and microspheres could increase the drug loading efficiency but decrease the drug entrapment efficiency. All these microspheres showed a restively higher drug loading efficiency at a pH value of about 7. The in
vitro drug release results showed that the drug release behavior of DOX-microspheres is characteristic with temperature-dependence. At about 37°C, DOX-microspheres show a relatively rapid release of DOX, and the prolonged release time of the drug on the microspheres was found when the cross linking density was increased. Using the DOX-microspheres as medicament, the animal test results showed that under the guidance of applied magnetic field, the DOX-microspheres could efficiently concentrated at the targeted tumor in the body of rats, and compared with pure DOX, the tumor inhibition effect of DOX-microspheres increased significantly, i.e. about five times higher than that of pure DOX. The side-effect of DOX-microspheres was also greatly reduced as a result of controlled release of DOX from microspheres in tumor. Furthermore, although the whole polymer microsphere is not biodegradable and biocompatible, almost no toxicity was found according to pathological test results. The animal test results reveal to us that the dual-responsive microspheres showed great application potential in the design of magnetically targeting drug delivery system for tumor therapy.(5) To further functonalization of dual-responsive polymer microspheres, a fluorescent molecules (fluorescein isothiocyanate, FITC) was incorporated into the silica shell of magnetite@silica, and through a preparation process similar to that for preparation of dual-responsive polymer microspheres, FITC-labeled dual-responsive polymer microspheres were prepared. As was characterized with transmission electron, scanning electron microscopy and atom force microscopy, the submicron sized microspheres showed nearly monodispersed size distribution, core-shell structure and spherical shape. Dynamic light scattering showed the microsphere possess thermoresponsive property, and the characterization results of fluorescence microscopy showed the obtained FITC-labeled dual-responsive microsphere had high luminescent intensity as a result of larger amount of FITC concentrated in the core of the microspheres. The fluorescent emission spectra of FITC, FITC-labeled magnetite@silica particles and FITC-labeled dual-responsive polymer microspheres demonstrated that the FITC molecules were successfully incorporated into the microspheres. Since the microspheres instigated the property of magnetic polymer
(1) 采用化学共沉淀法制备了超顺磁性的四氧化三铁纳米粒子的制备条件和工艺。
研究了影响化学共沉淀法制备四氧化三铁纳米粒子的各种因素,发现铁盐浓度、沉淀剂浓度以及沉淀剂与铁盐比例和反应温度均影响产物的性能。
最后通过采用分步升温加热的化学共沉淀法,制备了粒径大约15nm具有超顺磁性的四氧化三铁纳米粒子。
利用振动样品磁场计、X—射线衍射、透射电镜、红外等对产物进行了表征,证实了我们制备超顺磁性的四氧化三铁纳米粒子的方法的可靠性。
(2) 使用多元酸盐(柠檬酸三钠)成功地对四氧化三铁纳米粒子进行了表面改性,制备了电荷稳定的磁流体。研究了柠檬酸钠浓度对四氧化三铁纳米粒子改性效果的影响,发现在一定范围内加大柠檬酸钠用量可以使四氧化三铁纳米粒子分散稳定性逐渐增强。
利用改进的Stober法制备了不同形态的magnetite@silica复合粒子,发现通过调节柠檬酸钠对四氧化三铁纳米粒子的改性程度、控制前驱体TEOS的用量等可以控制magnetite@silica复合粒子的形态和粒径。使用TEM,DLS和SEM
Now with the research development in field of biomedicine and bioengineering, people are exploring various functional polymer microspheres which can serve as smart or intelligent tools for drug delivery, biomacromolecules purification, biosensor and enzyme immobilization,etc. Based on the research background and the development trend of polymer microspheres,the research interest of this work focused in the preparation and primary application of functionalized magnetic polymer microspheres, which involves in five parts, i.e. the preparation and surface modification of magnetite nanoparticles, preparation of magnetite@silica particles, preparation and primary application of dual-responsive polymer microspheres which possess magnetically responsive and thermoresponsive properties, and preparation of fluorescence labeled dual-responsive polymer microspheres. The results of each part are listed as follows:(1) Magnetite nanoparticles were prepared by chemical co-precipitation process. Different reaction parameters including reactant concentrate, reactant molar ratio and reaction temperature were found to dramatically influence the properties (particle size, superparamagnetic property, etc). Finally, superparamagnetic magnetite nanoparticles of about 15nm were obtained by using proper reactant concentrate, feeding ratios and controlling the reaction temperature increased stepwisely. The characterization results of vibrating sample magnetometer, X-ray diffraction and transmission electron microscope confirmed superparamagnetic magnetite particles with an average size of about 15nm were prepared.(2) By treating as-prepared magnetite nanoparticles with trisodium citrate aqueous solution, stable magnetic fluid (dispersion of magnetite nanoparticles in water) was prepared. It was found that, to some extent, more amount of trisodium citrate was used to modify the magnetite nanoparticles, more stable magnetic fluid was produced. Using the modified magnetite nanoparticles as seeds, silica-coated
magnetite particles (magnetite@silica) were prepared via a modified Stober method. It was found that the morphology of resulted magnet ite@si lie a particles is related with the extent of modification of magnetite. When magnetite particles modified with small amount of trisodium citrate were used as seeds, the magnetite@silica particles were silica-coated magnetite clusters, and when magnetite particles modified with larger amount of trisodium citrate were used as seeds, magnetite@silica shows a typical spherical shape and core-shell structure. The size of magnetite@silica particles is dependent of the amount of the precursor(tetraethyl orthosilicate).(3) Using magnetite@silica particle as seed, a dual-responsive polymer microsphere with core-shell structure was prepared by precipitation polymerization. The prepared microsphere consists of magnetite@silica core and crosslinked PNIPAM shell. The core of these microspheres could be tuned by using magnetite@silica particles of different size as seeds, and the crosslinking densities of the PNIPAM shell could be changed by changing the amount of crosslinker in the preparation recipes.The characterization results show that the prepared microspheres possesss magnetic property and thermoresponsive property, and the LCST of the microspheres could be tuned by changing the crosslinking density, when the crosslinking density of PNIPAM shell attained 25%,the LCST of the microsphere increased to 37°C. TEM and SEM observation shows that the size of the microspheres is in range of submicron scale. It is worthy noting that the method used in this study could be extended to prepare other inorganic-core-organic-shell polymer composite microspheres when various inorganic nanoparticles (Au, CdS, nanozeolite, etc.) are used, furthermore, other polymer could also be form on the surface of these inorganic particles through radical polymerization of corresponding monomers.(4)By using the prepared dual-responsive microspheres of different crosslinking densities(15%, 20% and 25%) as carrier of an anti-tumor drug (DOX), it was found that microspheres of higher cosslinking density possess lower drug loading capacity. Increasing the weight ratio between drug and microspheres could increase the drug loading efficiency but decrease the drug entrapment efficiency. All these microspheres showed a restively higher drug loading efficiency at a pH value of about 7. The in
vitro drug release results showed that the drug release behavior of DOX-microspheres is characteristic with temperature-dependence. At about 37°C, DOX-microspheres show a relatively rapid release of DOX, and the prolonged release time of the drug on the microspheres was found when the cross linking density was increased. Using the DOX-microspheres as medicament, the animal test results showed that under the guidance of applied magnetic field, the DOX-microspheres could efficiently concentrated at the targeted tumor in the body of rats, and compared with pure DOX, the tumor inhibition effect of DOX-microspheres increased significantly, i.e. about five times higher than that of pure DOX. The side-effect of DOX-microspheres was also greatly reduced as a result of controlled release of DOX from microspheres in tumor. Furthermore, although the whole polymer microsphere is not biodegradable and biocompatible, almost no toxicity was found according to pathological test results. The animal test results reveal to us that the dual-responsive microspheres showed great application potential in the design of magnetically targeting drug delivery system for tumor therapy.(5) To further functonalization of dual-responsive polymer microspheres, a fluorescent molecules (fluorescein isothiocyanate, FITC) was incorporated into the silica shell of magnetite@silica, and through a preparation process similar to that for preparation of dual-responsive polymer microspheres, FITC-labeled dual-responsive polymer microspheres were prepared. As was characterized with transmission electron, scanning electron microscopy and atom force microscopy, the submicron sized microspheres showed nearly monodispersed size distribution, core-shell structure and spherical shape. Dynamic light scattering showed the microsphere possess thermoresponsive property, and the characterization results of fluorescence microscopy showed the obtained FITC-labeled dual-responsive microsphere had high luminescent intensity as a result of larger amount of FITC concentrated in the core of the microspheres. The fluorescent emission spectra of FITC, FITC-labeled magnetite@silica particles and FITC-labeled dual-responsive polymer microspheres demonstrated that the FITC molecules were successfully incorporated into the microspheres. Since the microspheres instigated the property of magnetic polymer
引文
1. Roco M. C. Williams R. S., Alivisatos P. (editors), Interagency Working Group in Nanoscience Engineering and Technology (IWGN) Workshop Report, Nanotechnology Research Directions; Vision for Nanotechno[ogy R and D in the Next Decade, Published by Int. Tech. Research Institutes, WTEC Division, Loyola College, 1999, pp. ⅹⅹⅴ, 58, 118, 67, ⅹⅹⅶ, 70, 7, 102, 103.
2. Asua J. M. Polymeric dispersions; Principles and applications. Kluwer Academic Publishers, 1997, 515-539
3. Delair T H., Menier F., Elaissari A, et al. Amino-containing cationic latex-oligodeoxyribonucleotide conjugates, application to diagnostic test sensitivity enhancement. Colloid Surf A. 1999, 153, 341353.
4.徐如人,庞文琴,无机材料合成与制备化学.北京:高等教育出版社 2001,528-544
5.于德才,洪广言,共沉淀法制备铝酸镧超微粉末的研究,中国稀土学报,1992,10(1),44-48.
6.景晓燕,洪广言,李有漠,Y_2O_3稳定的ZrO_2超微粉的合成和结构研究,稀土,1989,10(4),4-7.
7. Qian Y T, Chen Q W, Chen Z Y, et al. Preparation of ultrafine powders of TiO_2 by hydrothermal H_2O_2 oxidation starting from metallic. J. Mater. Chem., 1993, 3, 203-205.
8. Chen Q, Qian Y, Zhang Y. Deagglomeration and crystallization of amorphous titiania by CCl4-thermal treatment, Mater Sci. Technol, 1996, 12, 211.
9. Dong X. T., Hong G. Y., et al. Synthesis and properties of Cerium Oxide Nanometer powders by pyrolysis of amorphous citrate. J Mater. Technol., 1997, 13, 113-116.
10. Papell S S, Method for preparation of stable magnetic fluid. US P 3 215 572, 1965.
11. Neuringer J L, Rosensweig R E. Phys. Fluids, 1964, 27, 1927.
12. Lefort J. Comptes Rendus Acad Sci. Paris, 1852, 34, 488.
13. Massart R. IEEE Trans Magnetics, 1981, 17(2), 1247.
14.邱广明,孙宗华.水溶性磁流体的制备和表征.化学试剂,1993,15(4),234-236.
15. Shen L F, Laibinis P E, Hatton T A. Bilayer surfactant stabilized magnetic fluids, Synthesis and interactions at interfaces. Langmuir 1999, 15, 447-453..
16. Molday R S, Mackenzie D J. Immunol Methods, 1982, 52, 353.
17. Harris L A, Goff J D, et al. Magnetite Nanoparticle Dispersions Stabilized with Triblock Copolymers. Chem. Mater. 2003, 15, 1367-1377.
18. Rockenberger J, Scher E C, Alivisatos P A. J Am Chem Soc, 1999, 121,11595.
19. Hyeon T, Lee S S, Park J, et al., J. Am. Chem. Soc., 2001, 123, 12798.
20. Guo Q, Teng X, Rahman S, et al. JAm Chem Soc, 2003, 125, 630.
21. Murray C B, Sun S, Gaschler W, et al. New aspects of nanocrystal research. IBM J Res & Dev, 2004, 45, 47.
22. Sun S, Murray C. B.. Synthesis of monodisperse cobalt nanocrystals and their assembly into magnetic superlattices. J. Appl. Phys., 1999, 85, 4325-4330.
23. Li Z, Chert H, Bao H, et al. One-Pot Reaction to Synthesize Water-Soluble Magnetite Nanocrystals. Chem. Mater., 2004, 16(8), 1391-1393.
24.谢钢,张秋禹,李铁虎.聚合物通报,2001,6,38.
25. Bahar T, Celibi S S. Immobilization of glucoamylase on magnetic poly(styrene) particles. J. Appl. Polym. Sci., 1999, 72, 69-73.
26. Yen S P S, Rembaum A, Landel R F. USP 4, 285, 819, 1981.
27. Emir B D, Ebru K, Cengiz B, Eylem O. React. Funct. Polym., 2002, 50, 225.
28.龚连生,周少波,张阳德.白蛋白阿霉素磁纳米粒在大鼠体内的生物分布.中国现代医学杂志,2001,11(3)8-10.
29.龚连生,张阳德,刘恕.磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性.中华肝胆外科杂志,2003,9,543-546.
30. Chatterjee J, Haik Y, Chen C J. Modification and characterization of polystyrene-based magnetic microspheres and comparison with albumin-based magnetic microspheres. J. Magn Magn Mater, 2001, 225, 21-29.
31. Goez-Lopera S A, Plaza R C. Synthesis and characterization of spherical magnetite/biodegradable polymer composite particles. Colloid Interface Sci, 2001, 240, 40-47.
32. Guesdon J, Avraemas L S. IMM, 1977, 14, 443.
33. Noguchi H, Yanase N, Uchida Y. Preparation and characterization by thermalanalysis of magnetic latex-particles J. Appl. Polym. Sci., 1993, 48, 1539-1547.
34. Xu X L, Friedman G, Humfeld K D, et al. Synthesis and utilization of monodisperse superparamagnetic colloidal particles for magnetically controllable photonic crystals. Chem Mater, 2002, 14, 1249-1256.
35. Dresco P A, Zaitsev V S, Gambio R J, et al. Preparation and properties of magnetite and polymer magnetite nanoparticles. Langmuir, 1999, 15, 1945-51.
36.邓勇辉,王雷,杨武利,等.反相微乳液合成30～100nm磁性聚合物纳米微球.高等学校化学学报,2003,24(5),920-924.
37. Deng Y, Wang L, Yang W, et al. Preparation of magnetic polymeric particles via inverse microemulsion polymerization process. J. Magn. Magn. Mater. 2003, 257 (1), 69-78.
38. Gupta A K, Wells S. Surface-modified superparamagnetic nanoparticles for drug delivery: Preparation, characterization, and cytotoxicity studies, IEEE Transcations on Nanobioscience, 2004, 3(1), 66-73.
39. Wormuth K. J. Superparamagnetic latex via inverse emulsion polymerization. Colloid Interface Sci., 2001, 241, 366-377.
40. Ramirez L P, Landfester K. Magnetic polystyrene nanoparticles with a high magnetite content obtained by miniemulsion processes. Macromol Chem Phys, 2003, 204, 22-31.
41. Landfester K. Adv. Mater. The generation of nanoparticles in miniemulsions, 2001, 13, 765-768.
42. Xu Z Z, Wang C C, Yang W L, et al. Encapsulation of nanosized magnetic iron oxide by polyacrylamide via inverse miniemulsion polymerization. J. Magn. Magn. Mater., 2004, 277, 136.
43. Xie G, Zhang Q Y, Luo Z P. Preparation and characterization of monodisperse magnetic poly(styrene butyl acrylate methacrylic acid) microspheres in the presence of a polar solvent. J. App. Polym. Sc., 2003, 87, 1733-1738.
44. Yanase N, Noguchi H, Asakura H, et al. J Appl Poly Sci,. Preparation of magnetic latex-particles by emulsion polymerization of styrene in the presence of a ferrofluid. 1993, 50, 765-776.
45. Bourgeat-Lami E, Espiard P. Guyot A. Poly(ethyl acrylate) latexes encapsulating nanoparticls of silica. 1. Fucntionalization and dispersion of silica. Polymer, 1995, 36(23), 4385-4389.
46. Jin L, Deng Y H, Hu J H, et al. Preparation and characterization of core-shell polymer particles with protonizable shells prepared by oxyanionic polymerization. J Polym Sci polym chem., 2004, 42, 6081-6088.
47. Sauzedde F, Elaissari A, Pichot C. Hydrophilic magnetic polymer latexes. 1. Adsorption of magnetic iron oxide nanoparticles onto various cationic latexes, Colloid Polym Sci, 1999, 277, 846-855.
48. Wang Y M, Wang Y, Feng L X. Preparation and magnetic properties of [P(St-co-AA)]Ni microspheres. J. Appl. Polym. Sci., 1997, 64, 1843-1848.
49. Wang Y M, Feng L X, Pen C. Characterization and magnetic properties of P(St-co-4VP) metal microspheres. J Appl Polym Sci, 1998, 70, 2307-2312.
50. Moore L R, Zborowski M. The use of magnetite-doped polymeric microspheres in calibrating cell tracking velocimetry. J. Biochem. Biophys Methods, 2000, 44, 115-130.
51. Sauzedde F, Elaissari A, Pichot C. Hydrophilic magnetic polymer latexes. 2. Encapsulation of adsorbed iron oxide nanoparticles. Colloid Polym Sci, 1999, 277, 1041-1050.
52. Furusawa K, Nagashima K, Anzai C. Synthetic process to control the total size and component distribution of multilayer magnetic composite-particles. Colloid Polym. Sci., 1994, 272, 1104-1110.
53. Horak D. Magnetic polyglycidylmethacrylate microspheres by dispersion polymerization. J. Polym. Sci. (Part A), Poly Chem, 2001, 39, 3707-3715.
54. Horak D, Nataliya B. Magnetic poly(glycidyl methacrylate) microspheres prepared by dispersion polymerization in the presence of electrostatically stabilized ferrofluids, J. Polym. Sci.(Part A) Polym Chem, 2004, 42, 5827-5837.
55. Horak D, Semenyuk N, Lednicky F. Effect of the reaction parameters on the particle size in the dispersion polymerization of 2-hydroxyethyl and glycidyl methacrylate in the presence of a ferrofluid. J. Polym. Sci. (Polym Chem Ed), 2003, 41, 1848-1863.
56. Horak D, Lednicky F, et al. Magnetic characteristics of ferrimagnetic microspheres prepared by dispersion polymerization. Macromo.l Mater. Eng. 2004, 289, 341-348.
57. Liu X Y, Ding X B, et al. Synthesis of novel magnetic polymer microspheres with amphiphilic structure. J. Appl. Poly Sci., 2003, 90, 1879-1884.
58.王艳君,刘江峰,姚兆玲,等.磁性聚甲基丙烯酸甲酯微球的制备与研究.天津大学学报,2001,34(1),64-68.
59.李孝红,丁小斌,孙宗华.含羟基磁性高分子微球的合成及表征.功能高分子学报,1995,8(1),73-76.
60.邱广明,高晓松,杨春雁,等.聚合物乳液通讯,1995,15(2),11.
61.罗正平,张秋禹,吴昊,等.微米级PSt,P(St/MAA)磁性高分子微球的合成Ⅰ.温度、引发剂、介质极性、稳定剂量的影响.功能高分子学报,2002,15(2),147-152.
62. Rembaum A. USP, 4, 267, 234, 1981.
63. Liu X Q, Guan Y P. Synthesis and properties of micron-size magnetic polymer spheres with epoxy groups. Chin J. Chem. Engin., 2003, 11 (6), 731-735.
64. Lee Y, Rho J, Jung B. Preparation of magnetic ion-exchange resins by the suspension polymerization of styrene with magnetite. J Appl Poly Sci, 2003, 89 (8), 2058-2067.
65.万惠文,张强,宋宏涛,等.聚合物磁性粒子的制备.武汉工业大学学报,1999,21(1),22-25.
66.王胜林,朱以华,吴秋芳,等.微悬浮聚合法合成聚苯乙烯磁性微球.华东理工大学学报,2001,27(4),364-368.
67. Ugelstad J, Ellingsen T, Berge A, et. al. US P, 4, 774, 265, 1988.
68. Lindlar B, Boldt M, Eiden-Assmann S, Maret G.. Synthesis of monodisperse magnetic methacrylate polymer particles. Adv. Mater., 2004, 14, 1656-1658.
69. Zhang J, Coombs N, Kumacheva E. Polymer Microgels: Reactors for Semiconductor, Metal, and Magnetic Nanoparticles. J. Am. Chem. Soc., 2004, 126, 7908.
70. Christy R V, Zhang Z J. Atom Transfer Radical Polymerization Synthesis and Magnetic Characterization of MnFe_2O_4/Polystyrene Core/Shell Nanoparticles. J. Am. Chem. Soc., 2002, 124, 14312-14313.
71. Nicholas A D, Burke H, Stover D H, et al. Magnetic Nanocomposites: Preparation and Characterization of Polymer-Coated Iron Nanoparticles. Chem Mater, 2002, 14, 4752-4761.
72. Okubo M, Minami H, Komura T. Preparation of micrometer-sized, monodisperse, magnetic polymer particles. J. Appl. Polym. Sci., 2003, 88, 428-433.
73. Safarik I, Safarikova M. Magnetic nanoparticles and biosciences. Mon. Chem., 2002, 133, 737-759.
74. Fricker J. Drugs with a magnetic attraction to tumours. Drug Discov. Today, 2001, 6(8), 387-389.
75. Schutt W, Gruttner C, Teller J, et al. Biocompatible magnetic polymer carriers for in vivo radionuclide delivery. Artif Organs, 1999, 23, 98-103.
76. Molday R S, Yen S P S, Rembaum A. Nature, 1977, 268, 437.
77. Rembaum A, Dreyer W J. Science, 1980, 208, 364.
78. Senyei A E, Widder K J. USP, 4 230 685, 1980.
79. Ugelstad J, Stenstad P, Kilaas L, et al. USP, 5, 763, 203, 1998.
80. Josephson L. USP, 4, 672, 040, 1987.
81.吴传斌,何素梅,高文伟,等.阿霉素磁性明胶微球的制备及特性研究.中国医药工业杂志,1994,25(2),63-66.
82. Wilson R J, USP, 5, 932, 097, 1999.
83. Katharine M P, Eric J J, Graham A. J Immuno Meth, 1999, 223, 195.
84. Safarik I, Safarikova M, J Chromatogr B Biomed Sci Appl, 1999, 722, 33.
85. Safarik I, Safarikova M, Cells isolation, magnetic techniques. In Encyclopedia of Separation Science (Edited by, Wilson ID, Adlard TR, Poole CF, Cool M). London, Academic Press, 2000, 2260.
86. Mosbach K, Andersson L. Nature, 1977, 270, 259.
87. Whitehead R A, Chagnon M S, Groman E V, et al. USP 4, 554, 088, 1985.
88. Lochmuller C H. Wigman L S. Separation Sci Technol, 1987, 22 (11), 2111.
89. Hubbuch J J, Thomas Ort. High-gradient magnetic affinity separation of trypsin from porcine pancreatin. Biotechnol and Bioengin, 2002, 79(3), 301-313.
90. Xu H, Zhang G L, Zhang F B, et al. Study on removal of bilirubin with magnetic affinity separation technique. Chin J Chem Engin, 2003, 11 (4), 456-459.
91. Frenzel A, Bergemann C, Kohl G, et al. Novel purification system for 6xHis-tagged proteins by magnetic affinity separation. J Chromatogr B, 2003, 793 (2), 325-329.
92. Uhlen M. Nature, 1989, 340, 733.
93. Peter R L, Stephen E B. J. Chromato A, 1998, 816, 107.
94. Bach H J, Hartmann A, Trevors J T, et al Magnetic capture-hybridization method for purification and probing of mRNA for neutral protease of Bacillus cereus. J Microbio Meth, 1999, 37, 187-192.
95. Weizmann Y, Patolsky F, Lioubashevski O, et al. Magneto-mechanical detection of nucleic acids and telomerase activity in cancer cells. J. Am. Chem. Soc., 2004, 126(4), 1073-1080.
96. Horak D, Rittich B, Safar J, et al. Properties of RNase a immobilized on magnetic poly(2-hydroxyethyl methacrylate) microspheres. Biotechnol Prog, 2001, 17(3), 447-452.
97. Chen J P, Su D R. Latex particles with thermo-flocculation and magnetic properties for immobilization of alpha-chymotrypsin. Biotechnol Prog, 2001, 17(2), 369-375.
98. Rana S, White P, Bradley M. Synthesis of magnetic beads for solid phase synthesis and reaction scavenging. Tetrahedron Letters, 1999, 40, 8137-8140.
99. Benner SA. EP 113, 452, 1984.
100. Scholeiki I. USP 5, 684, 130, 1997.
101. Sucholeiki I. USP 5, 858, 534, 1999.
102. Hirsch R, Katz E, Willner I. et al. J. Am. Chem. Soc., Magneto-switchable bioelectrocatalysis, 2000, 122(48), 12053-12054.
103. Weizmann Y, Patolsky F, Katz E, et al. Amplified DNA sensing and immunosensing by the rotation of functional magnetic particles. J Am Chem Soc, 2003, 125 (12), 3452-3454.
104. Katz E, Willner I. J Am Chem Soc. Magneto-stimulated hydrodynamic control of electrocatalytic and bioelectrocatalytic processes, 2002, 124 (35), 10290-10291.
105. Skjerve E, Olsvik O. Int. J Food Microbiol. Immunomagnetic separation of salmonella from foods, 1991, 14, 11-17.
106. Bruno J G, Yu H. Appl. Environ. Microbiol. Immunomagnetic-electrochemiluminescent detection of Bacillus anthracis spores in soil matrices, 1996, 62 (9), 3474-3476.
107. Yu H. Anal Chem Acta. Use of an immunomagnetic separation-fluorescent immunoassay (IMS-FIA) for rapid and high throughput analysis of environmental water samples, 1998, 376, 77-81.
108. Sylvie H S, Emmanuelle G. FEMS Microbiology Letters, 1999, 176, 285.
109. Nakamura M, Decker K, Chosy J, et al. Separation of a breast cancer cell line from human blood using a quadrupole magnetic flow sorter. Biotechnol. Prog, 2001, 17(6), 1145-1155.
110. Andreas T, Alexander S, Andreas R. Immunotechnol, 1998, 4, 89.
111. Safarik I, Safarikova M. J. Chromatogr B. Use of magnetic techniques for the isolation of cells, 1999, 722, 33-53.
112. Poynton C H. USP 4, 920, 061. 1990.
113. Bjerke T, Nielsen S, Uglestad J, et al. J. Immunol. Meth. Purification of human blood basophils by negative selection using immunomagnetic beads, 1993, 157, 49-56.
114. Rembaum A, Dreyer W J, Science, 1980, 208, 364.
115. Durcova G., Tokunaga T, Takahasi S, et al. Theriogenology, 1997, 47, 242.
116. Ugelstad J, Berge A, Ellingsen T, et al Preparation and application of new monosized polymer particles. Prog Polym Sci, 1992, 17, 87-161.
117.邱广明,孙宗华.磁性高分子微球共价结合中性蛋白酶.生物医学工程杂志,1995,12(3),209-213.
118.邱广亮,张艳茹.磁性载体用于酶固定化方面的研究.内蒙古师范大学学报,1998,27(2),129-133.
119. Zuzana B, Marcela S, et al. J. Chromatogr. B. Oriented immobilization of galactose oxidase to bead and magnetic bead cellulose and poly(HEMA-co-EDMA) and magnetic poly(HEMA-co-EDMA) microspheres, 2002, 770, 25-34.
120. Freeman M W, J Appl Phys, 1960, 31 (5), 404.
121. Myas S P, Sihorkar V. J. Microencapsul. , 1989, 6 (4), 493.
122. Wu C B, Wei S L, He SM. J. Clin. Pharm. Sci, 1995, 4, 1.
123. Jones S K, Winter J G. Experimental examination of a targeted hyperthermia system using inductively heated ferromagnetic microspheres in rabbit kidney. Phys. Med. Biol, 2001, 46, 385-398.
124. Lubbe A S, Bergemann C, Riess H. Clinical experiences with magnetic drag targeting, A phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors. Cancer Res, 1996, 56, 4686-4693.
125.张阳德,龚连生.阿霉素白蛋白磁纳米粒在正常肝脏的靶向性.中国现代医学杂志,2001,11,4-7.
126.张阳德,王荣兵,龚连生,等.半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药物动力学研究.中国医学工程.2004,12 (3) 9:4-8.
127. Hafeli U O. , Magnetically modulated therapeutic systems International Journal of Pharmaceutics, 2004, 277, 19-24.
128. Oster J. , Parker J. , Brassard L. Polyvinyl-alcohol-based magnetic beads for rapid and efficient separation of specific or unspecific nucleic acid sequences J. Magn. Magn. Mater. 2001, 225, 145-150.
129. Pelton R H. , Chibante P. Preparation of aqueous latices with N-isopropylacrylamide, Colloids Surfaces. 1986, 20, 247-256.
130. Meunier. F, Elassari A. In Colloidal polymer: synthesis and characterization, New York, Marcel Dekker, INC. 2004, p117-144.
131. Mcphee W. , Tam K. C. , Pelton R. Poly(N-isopropylacrylamide) latices prepared with sodium dodecyl-sulfate. J. Colloid Interface Sci. , 1993, 156, 24-30.
132. Nagaoka N. , Kubota H. , Safrani A. , et al. Synthesis of poly(N-isopropyl-acrylamide) hydrogels by radiation polymerization and cross-linking. Macromolecules, 1993, 26, 7386-7388.
133. Park T. G. , Hoffman A. S. , J. Polym. Sci. Part A, Polym. Chem. 1992, 30, 505.
134. Zhou S. , Chu B. , J. Phys. Chem. Synthesis and Volume Phase Transition of Poly(methacrylic acid-co-N-isopropylacrylamide) Microgel Particles in Water, 1998, 102, 1364-1371.
135. Kratz K. , Hellweg T. , Eimer W. Influence of charge density on the swelling of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels. Colloids Surf A. , 2000, 170, 137-149.
136. Yu H. , Grainger D. W. Thermosensitive sweeling behavior in crossliked N-isopropylamide networks-cationic, anionic, and ampholytic hydrogels, J. Appl. Polym. Sci. , 1993, 49, 1553-1563.
137. Xiao X. C. , Chu L. Y. , Chen W. M. , Monodispersed thermoresponsive hydrogel microspheres with a volume phase transition driven byhydrogen bonding. Polymer, 2005, 46, 3199-3209.
138. Hoffman A. S. J. Controlled Release, 1987, 6, 297.
139. Emanuele A. D. , Dinarvand R. Preparation, Characterisation, and drug release from thermoresponsive microspheres. International Journal Pharmaceutics, 1995, 118, 237-242.
140. Kim I. S. , Jeong Y. I. , Kim S. H. , et al. Archives of phamacal research. Drug release from thermo-responsive self-assembled polymeric micelles composed of cholic acid and poly(N-isopropylacrylamide), 2000, 23, 367-373.
141. Elmas B. , Onur M. A. , Sene S. , et al. Thermosensitive N-isopropylacrylamide-vinylphenyl boronic acid copolymer latex particles for nucleotide isolation. Colloids and Surfaces A. , 2004, 232, 253-259.
142. Kawaguchi H. , Fujimoto K. , Mizuhara Y. Hydrogel microspheres. 3.
2. Asua J. M. Polymeric dispersions; Principles and applications. Kluwer Academic Publishers, 1997, 515-539
3. Delair T H., Menier F., Elaissari A, et al. Amino-containing cationic latex-oligodeoxyribonucleotide conjugates, application to diagnostic test sensitivity enhancement. Colloid Surf A. 1999, 153, 341353.
4.徐如人,庞文琴,无机材料合成与制备化学.北京:高等教育出版社 2001,528-544
5.于德才,洪广言,共沉淀法制备铝酸镧超微粉末的研究,中国稀土学报,1992,10(1),44-48.
6.景晓燕,洪广言,李有漠,Y_2O_3稳定的ZrO_2超微粉的合成和结构研究,稀土,1989,10(4),4-7.
7. Qian Y T, Chen Q W, Chen Z Y, et al. Preparation of ultrafine powders of TiO_2 by hydrothermal H_2O_2 oxidation starting from metallic. J. Mater. Chem., 1993, 3, 203-205.
8. Chen Q, Qian Y, Zhang Y. Deagglomeration and crystallization of amorphous titiania by CCl4-thermal treatment, Mater Sci. Technol, 1996, 12, 211.
9. Dong X. T., Hong G. Y., et al. Synthesis and properties of Cerium Oxide Nanometer powders by pyrolysis of amorphous citrate. J Mater. Technol., 1997, 13, 113-116.
10. Papell S S, Method for preparation of stable magnetic fluid. US P 3 215 572, 1965.
11. Neuringer J L, Rosensweig R E. Phys. Fluids, 1964, 27, 1927.
12. Lefort J. Comptes Rendus Acad Sci. Paris, 1852, 34, 488.
13. Massart R. IEEE Trans Magnetics, 1981, 17(2), 1247.
14.邱广明,孙宗华.水溶性磁流体的制备和表征.化学试剂,1993,15(4),234-236.
15. Shen L F, Laibinis P E, Hatton T A. Bilayer surfactant stabilized magnetic fluids, Synthesis and interactions at interfaces. Langmuir 1999, 15, 447-453..
16. Molday R S, Mackenzie D J. Immunol Methods, 1982, 52, 353.
17. Harris L A, Goff J D, et al. Magnetite Nanoparticle Dispersions Stabilized with Triblock Copolymers. Chem. Mater. 2003, 15, 1367-1377.
18. Rockenberger J, Scher E C, Alivisatos P A. J Am Chem Soc, 1999, 121,11595.
19. Hyeon T, Lee S S, Park J, et al., J. Am. Chem. Soc., 2001, 123, 12798.
20. Guo Q, Teng X, Rahman S, et al. JAm Chem Soc, 2003, 125, 630.
21. Murray C B, Sun S, Gaschler W, et al. New aspects of nanocrystal research. IBM J Res & Dev, 2004, 45, 47.
22. Sun S, Murray C. B.. Synthesis of monodisperse cobalt nanocrystals and their assembly into magnetic superlattices. J. Appl. Phys., 1999, 85, 4325-4330.
23. Li Z, Chert H, Bao H, et al. One-Pot Reaction to Synthesize Water-Soluble Magnetite Nanocrystals. Chem. Mater., 2004, 16(8), 1391-1393.
24.谢钢,张秋禹,李铁虎.聚合物通报,2001,6,38.
25. Bahar T, Celibi S S. Immobilization of glucoamylase on magnetic poly(styrene) particles. J. Appl. Polym. Sci., 1999, 72, 69-73.
26. Yen S P S, Rembaum A, Landel R F. USP 4, 285, 819, 1981.
27. Emir B D, Ebru K, Cengiz B, Eylem O. React. Funct. Polym., 2002, 50, 225.
28.龚连生,周少波,张阳德.白蛋白阿霉素磁纳米粒在大鼠体内的生物分布.中国现代医学杂志,2001,11(3)8-10.
29.龚连生,张阳德,刘恕.磁性阿霉素白蛋白纳米粒在移植性肝癌模型中的磁靶向性.中华肝胆外科杂志,2003,9,543-546.
30. Chatterjee J, Haik Y, Chen C J. Modification and characterization of polystyrene-based magnetic microspheres and comparison with albumin-based magnetic microspheres. J. Magn Magn Mater, 2001, 225, 21-29.
31. Goez-Lopera S A, Plaza R C. Synthesis and characterization of spherical magnetite/biodegradable polymer composite particles. Colloid Interface Sci, 2001, 240, 40-47.
32. Guesdon J, Avraemas L S. IMM, 1977, 14, 443.
33. Noguchi H, Yanase N, Uchida Y. Preparation and characterization by thermalanalysis of magnetic latex-particles J. Appl. Polym. Sci., 1993, 48, 1539-1547.
34. Xu X L, Friedman G, Humfeld K D, et al. Synthesis and utilization of monodisperse superparamagnetic colloidal particles for magnetically controllable photonic crystals. Chem Mater, 2002, 14, 1249-1256.
35. Dresco P A, Zaitsev V S, Gambio R J, et al. Preparation and properties of magnetite and polymer magnetite nanoparticles. Langmuir, 1999, 15, 1945-51.
36.邓勇辉,王雷,杨武利,等.反相微乳液合成30～100nm磁性聚合物纳米微球.高等学校化学学报,2003,24(5),920-924.
37. Deng Y, Wang L, Yang W, et al. Preparation of magnetic polymeric particles via inverse microemulsion polymerization process. J. Magn. Magn. Mater. 2003, 257 (1), 69-78.
38. Gupta A K, Wells S. Surface-modified superparamagnetic nanoparticles for drug delivery: Preparation, characterization, and cytotoxicity studies, IEEE Transcations on Nanobioscience, 2004, 3(1), 66-73.
39. Wormuth K. J. Superparamagnetic latex via inverse emulsion polymerization. Colloid Interface Sci., 2001, 241, 366-377.
40. Ramirez L P, Landfester K. Magnetic polystyrene nanoparticles with a high magnetite content obtained by miniemulsion processes. Macromol Chem Phys, 2003, 204, 22-31.
41. Landfester K. Adv. Mater. The generation of nanoparticles in miniemulsions, 2001, 13, 765-768.
42. Xu Z Z, Wang C C, Yang W L, et al. Encapsulation of nanosized magnetic iron oxide by polyacrylamide via inverse miniemulsion polymerization. J. Magn. Magn. Mater., 2004, 277, 136.
43. Xie G, Zhang Q Y, Luo Z P. Preparation and characterization of monodisperse magnetic poly(styrene butyl acrylate methacrylic acid) microspheres in the presence of a polar solvent. J. App. Polym. Sc., 2003, 87, 1733-1738.
44. Yanase N, Noguchi H, Asakura H, et al. J Appl Poly Sci,. Preparation of magnetic latex-particles by emulsion polymerization of styrene in the presence of a ferrofluid. 1993, 50, 765-776.
45. Bourgeat-Lami E, Espiard P. Guyot A. Poly(ethyl acrylate) latexes encapsulating nanoparticls of silica. 1. Fucntionalization and dispersion of silica. Polymer, 1995, 36(23), 4385-4389.
46. Jin L, Deng Y H, Hu J H, et al. Preparation and characterization of core-shell polymer particles with protonizable shells prepared by oxyanionic polymerization. J Polym Sci polym chem., 2004, 42, 6081-6088.
47. Sauzedde F, Elaissari A, Pichot C. Hydrophilic magnetic polymer latexes. 1. Adsorption of magnetic iron oxide nanoparticles onto various cationic latexes, Colloid Polym Sci, 1999, 277, 846-855.
48. Wang Y M, Wang Y, Feng L X. Preparation and magnetic properties of [P(St-co-AA)]Ni microspheres. J. Appl. Polym. Sci., 1997, 64, 1843-1848.
49. Wang Y M, Feng L X, Pen C. Characterization and magnetic properties of P(St-co-4VP) metal microspheres. J Appl Polym Sci, 1998, 70, 2307-2312.
50. Moore L R, Zborowski M. The use of magnetite-doped polymeric microspheres in calibrating cell tracking velocimetry. J. Biochem. Biophys Methods, 2000, 44, 115-130.
51. Sauzedde F, Elaissari A, Pichot C. Hydrophilic magnetic polymer latexes. 2. Encapsulation of adsorbed iron oxide nanoparticles. Colloid Polym Sci, 1999, 277, 1041-1050.
52. Furusawa K, Nagashima K, Anzai C. Synthetic process to control the total size and component distribution of multilayer magnetic composite-particles. Colloid Polym. Sci., 1994, 272, 1104-1110.
53. Horak D. Magnetic polyglycidylmethacrylate microspheres by dispersion polymerization. J. Polym. Sci. (Part A), Poly Chem, 2001, 39, 3707-3715.
54. Horak D, Nataliya B. Magnetic poly(glycidyl methacrylate) microspheres prepared by dispersion polymerization in the presence of electrostatically stabilized ferrofluids, J. Polym. Sci.(Part A) Polym Chem, 2004, 42, 5827-5837.
55. Horak D, Semenyuk N, Lednicky F. Effect of the reaction parameters on the particle size in the dispersion polymerization of 2-hydroxyethyl and glycidyl methacrylate in the presence of a ferrofluid. J. Polym. Sci. (Polym Chem Ed), 2003, 41, 1848-1863.
56. Horak D, Lednicky F, et al. Magnetic characteristics of ferrimagnetic microspheres prepared by dispersion polymerization. Macromo.l Mater. Eng. 2004, 289, 341-348.
57. Liu X Y, Ding X B, et al. Synthesis of novel magnetic polymer microspheres with amphiphilic structure. J. Appl. Poly Sci., 2003, 90, 1879-1884.
58.王艳君,刘江峰,姚兆玲,等.磁性聚甲基丙烯酸甲酯微球的制备与研究.天津大学学报,2001,34(1),64-68.
59.李孝红,丁小斌,孙宗华.含羟基磁性高分子微球的合成及表征.功能高分子学报,1995,8(1),73-76.
60.邱广明,高晓松,杨春雁,等.聚合物乳液通讯,1995,15(2),11.
61.罗正平,张秋禹,吴昊,等.微米级PSt,P(St/MAA)磁性高分子微球的合成Ⅰ.温度、引发剂、介质极性、稳定剂量的影响.功能高分子学报,2002,15(2),147-152.
62. Rembaum A. USP, 4, 267, 234, 1981.
63. Liu X Q, Guan Y P. Synthesis and properties of micron-size magnetic polymer spheres with epoxy groups. Chin J. Chem. Engin., 2003, 11 (6), 731-735.
64. Lee Y, Rho J, Jung B. Preparation of magnetic ion-exchange resins by the suspension polymerization of styrene with magnetite. J Appl Poly Sci, 2003, 89 (8), 2058-2067.
65.万惠文,张强,宋宏涛,等.聚合物磁性粒子的制备.武汉工业大学学报,1999,21(1),22-25.
66.王胜林,朱以华,吴秋芳,等.微悬浮聚合法合成聚苯乙烯磁性微球.华东理工大学学报,2001,27(4),364-368.
67. Ugelstad J, Ellingsen T, Berge A, et. al. US P, 4, 774, 265, 1988.
68. Lindlar B, Boldt M, Eiden-Assmann S, Maret G.. Synthesis of monodisperse magnetic methacrylate polymer particles. Adv. Mater., 2004, 14, 1656-1658.
69. Zhang J, Coombs N, Kumacheva E. Polymer Microgels: Reactors for Semiconductor, Metal, and Magnetic Nanoparticles. J. Am. Chem. Soc., 2004, 126, 7908.
70. Christy R V, Zhang Z J. Atom Transfer Radical Polymerization Synthesis and Magnetic Characterization of MnFe_2O_4/Polystyrene Core/Shell Nanoparticles. J. Am. Chem. Soc., 2002, 124, 14312-14313.
71. Nicholas A D, Burke H, Stover D H, et al. Magnetic Nanocomposites: Preparation and Characterization of Polymer-Coated Iron Nanoparticles. Chem Mater, 2002, 14, 4752-4761.
72. Okubo M, Minami H, Komura T. Preparation of micrometer-sized, monodisperse, magnetic polymer particles. J. Appl. Polym. Sci., 2003, 88, 428-433.
73. Safarik I, Safarikova M. Magnetic nanoparticles and biosciences. Mon. Chem., 2002, 133, 737-759.
74. Fricker J. Drugs with a magnetic attraction to tumours. Drug Discov. Today, 2001, 6(8), 387-389.
75. Schutt W, Gruttner C, Teller J, et al. Biocompatible magnetic polymer carriers for in vivo radionuclide delivery. Artif Organs, 1999, 23, 98-103.
76. Molday R S, Yen S P S, Rembaum A. Nature, 1977, 268, 437.
77. Rembaum A, Dreyer W J. Science, 1980, 208, 364.
78. Senyei A E, Widder K J. USP, 4 230 685, 1980.
79. Ugelstad J, Stenstad P, Kilaas L, et al. USP, 5, 763, 203, 1998.
80. Josephson L. USP, 4, 672, 040, 1987.
81.吴传斌,何素梅,高文伟,等.阿霉素磁性明胶微球的制备及特性研究.中国医药工业杂志,1994,25(2),63-66.
82. Wilson R J, USP, 5, 932, 097, 1999.
83. Katharine M P, Eric J J, Graham A. J Immuno Meth, 1999, 223, 195.
84. Safarik I, Safarikova M, J Chromatogr B Biomed Sci Appl, 1999, 722, 33.
85. Safarik I, Safarikova M, Cells isolation, magnetic techniques. In Encyclopedia of Separation Science (Edited by, Wilson ID, Adlard TR, Poole CF, Cool M). London, Academic Press, 2000, 2260.
86. Mosbach K, Andersson L. Nature, 1977, 270, 259.
87. Whitehead R A, Chagnon M S, Groman E V, et al. USP 4, 554, 088, 1985.
88. Lochmuller C H. Wigman L S. Separation Sci Technol, 1987, 22 (11), 2111.
89. Hubbuch J J, Thomas Ort. High-gradient magnetic affinity separation of trypsin from porcine pancreatin. Biotechnol and Bioengin, 2002, 79(3), 301-313.
90. Xu H, Zhang G L, Zhang F B, et al. Study on removal of bilirubin with magnetic affinity separation technique. Chin J Chem Engin, 2003, 11 (4), 456-459.
91. Frenzel A, Bergemann C, Kohl G, et al. Novel purification system for 6xHis-tagged proteins by magnetic affinity separation. J Chromatogr B, 2003, 793 (2), 325-329.
92. Uhlen M. Nature, 1989, 340, 733.
93. Peter R L, Stephen E B. J. Chromato A, 1998, 816, 107.
94. Bach H J, Hartmann A, Trevors J T, et al Magnetic capture-hybridization method for purification and probing of mRNA for neutral protease of Bacillus cereus. J Microbio Meth, 1999, 37, 187-192.
95. Weizmann Y, Patolsky F, Lioubashevski O, et al. Magneto-mechanical detection of nucleic acids and telomerase activity in cancer cells. J. Am. Chem. Soc., 2004, 126(4), 1073-1080.
96. Horak D, Rittich B, Safar J, et al. Properties of RNase a immobilized on magnetic poly(2-hydroxyethyl methacrylate) microspheres. Biotechnol Prog, 2001, 17(3), 447-452.
97. Chen J P, Su D R. Latex particles with thermo-flocculation and magnetic properties for immobilization of alpha-chymotrypsin. Biotechnol Prog, 2001, 17(2), 369-375.
98. Rana S, White P, Bradley M. Synthesis of magnetic beads for solid phase synthesis and reaction scavenging. Tetrahedron Letters, 1999, 40, 8137-8140.
99. Benner SA. EP 113, 452, 1984.
100. Scholeiki I. USP 5, 684, 130, 1997.
101. Sucholeiki I. USP 5, 858, 534, 1999.
102. Hirsch R, Katz E, Willner I. et al. J. Am. Chem. Soc., Magneto-switchable bioelectrocatalysis, 2000, 122(48), 12053-12054.
103. Weizmann Y, Patolsky F, Katz E, et al. Amplified DNA sensing and immunosensing by the rotation of functional magnetic particles. J Am Chem Soc, 2003, 125 (12), 3452-3454.
104. Katz E, Willner I. J Am Chem Soc. Magneto-stimulated hydrodynamic control of electrocatalytic and bioelectrocatalytic processes, 2002, 124 (35), 10290-10291.
105. Skjerve E, Olsvik O. Int. J Food Microbiol. Immunomagnetic separation of salmonella from foods, 1991, 14, 11-17.
106. Bruno J G, Yu H. Appl. Environ. Microbiol. Immunomagnetic-electrochemiluminescent detection of Bacillus anthracis spores in soil matrices, 1996, 62 (9), 3474-3476.
107. Yu H. Anal Chem Acta. Use of an immunomagnetic separation-fluorescent immunoassay (IMS-FIA) for rapid and high throughput analysis of environmental water samples, 1998, 376, 77-81.
108. Sylvie H S, Emmanuelle G. FEMS Microbiology Letters, 1999, 176, 285.
109. Nakamura M, Decker K, Chosy J, et al. Separation of a breast cancer cell line from human blood using a quadrupole magnetic flow sorter. Biotechnol. Prog, 2001, 17(6), 1145-1155.
110. Andreas T, Alexander S, Andreas R. Immunotechnol, 1998, 4, 89.
111. Safarik I, Safarikova M. J. Chromatogr B. Use of magnetic techniques for the isolation of cells, 1999, 722, 33-53.
112. Poynton C H. USP 4, 920, 061. 1990.
113. Bjerke T, Nielsen S, Uglestad J, et al. J. Immunol. Meth. Purification of human blood basophils by negative selection using immunomagnetic beads, 1993, 157, 49-56.
114. Rembaum A, Dreyer W J, Science, 1980, 208, 364.
115. Durcova G., Tokunaga T, Takahasi S, et al. Theriogenology, 1997, 47, 242.
116. Ugelstad J, Berge A, Ellingsen T, et al Preparation and application of new monosized polymer particles. Prog Polym Sci, 1992, 17, 87-161.
117.邱广明,孙宗华.磁性高分子微球共价结合中性蛋白酶.生物医学工程杂志,1995,12(3),209-213.
118.邱广亮,张艳茹.磁性载体用于酶固定化方面的研究.内蒙古师范大学学报,1998,27(2),129-133.
119. Zuzana B, Marcela S, et al. J. Chromatogr. B. Oriented immobilization of galactose oxidase to bead and magnetic bead cellulose and poly(HEMA-co-EDMA) and magnetic poly(HEMA-co-EDMA) microspheres, 2002, 770, 25-34.
120. Freeman M W, J Appl Phys, 1960, 31 (5), 404.
121. Myas S P, Sihorkar V. J. Microencapsul. , 1989, 6 (4), 493.
122. Wu C B, Wei S L, He SM. J. Clin. Pharm. Sci, 1995, 4, 1.
123. Jones S K, Winter J G. Experimental examination of a targeted hyperthermia system using inductively heated ferromagnetic microspheres in rabbit kidney. Phys. Med. Biol, 2001, 46, 385-398.
124. Lubbe A S, Bergemann C, Riess H. Clinical experiences with magnetic drag targeting, A phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors. Cancer Res, 1996, 56, 4686-4693.
125.张阳德,龚连生.阿霉素白蛋白磁纳米粒在正常肝脏的靶向性.中国现代医学杂志,2001,11,4-7.
126.张阳德,王荣兵,龚连生,等.半乳糖化白蛋白磁性阿霉素纳米粒在家兔体内的药物动力学研究.中国医学工程.2004,12 (3) 9:4-8.
127. Hafeli U O. , Magnetically modulated therapeutic systems International Journal of Pharmaceutics, 2004, 277, 19-24.
128. Oster J. , Parker J. , Brassard L. Polyvinyl-alcohol-based magnetic beads for rapid and efficient separation of specific or unspecific nucleic acid sequences J. Magn. Magn. Mater. 2001, 225, 145-150.
129. Pelton R H. , Chibante P. Preparation of aqueous latices with N-isopropylacrylamide, Colloids Surfaces. 1986, 20, 247-256.
130. Meunier. F, Elassari A. In Colloidal polymer: synthesis and characterization, New York, Marcel Dekker, INC. 2004, p117-144.
131. Mcphee W. , Tam K. C. , Pelton R. Poly(N-isopropylacrylamide) latices prepared with sodium dodecyl-sulfate. J. Colloid Interface Sci. , 1993, 156, 24-30.
132. Nagaoka N. , Kubota H. , Safrani A. , et al. Synthesis of poly(N-isopropyl-acrylamide) hydrogels by radiation polymerization and cross-linking. Macromolecules, 1993, 26, 7386-7388.
133. Park T. G. , Hoffman A. S. , J. Polym. Sci. Part A, Polym. Chem. 1992, 30, 505.
134. Zhou S. , Chu B. , J. Phys. Chem. Synthesis and Volume Phase Transition of Poly(methacrylic acid-co-N-isopropylacrylamide) Microgel Particles in Water, 1998, 102, 1364-1371.
135. Kratz K. , Hellweg T. , Eimer W. Influence of charge density on the swelling of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels. Colloids Surf A. , 2000, 170, 137-149.
136. Yu H. , Grainger D. W. Thermosensitive sweeling behavior in crossliked N-isopropylamide networks-cationic, anionic, and ampholytic hydrogels, J. Appl. Polym. Sci. , 1993, 49, 1553-1563.
137. Xiao X. C. , Chu L. Y. , Chen W. M. , Monodispersed thermoresponsive hydrogel microspheres with a volume phase transition driven byhydrogen bonding. Polymer, 2005, 46, 3199-3209.
138. Hoffman A. S. J. Controlled Release, 1987, 6, 297.
139. Emanuele A. D. , Dinarvand R. Preparation, Characterisation, and drug release from thermoresponsive microspheres. International Journal Pharmaceutics, 1995, 118, 237-242.
140. Kim I. S. , Jeong Y. I. , Kim S. H. , et al. Archives of phamacal research. Drug release from thermo-responsive self-assembled polymeric micelles composed of cholic acid and poly(N-isopropylacrylamide), 2000, 23, 367-373.
141. Elmas B. , Onur M. A. , Sene S. , et al. Thermosensitive N-isopropylacrylamide-vinylphenyl boronic acid copolymer latex particles for nucleotide isolation. Colloids and Surfaces A. , 2004, 232, 253-259.
142. Kawaguchi H. , Fujimoto K. , Mizuhara Y. Hydrogel microspheres. 3.