超顺磁性Fe_3O_4纳米粒子的合成、修饰及其与DNA相互作用的研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
第一章:综述了磁性四氧化三铁纳米粒子的合成方法及其在生物医药领域的应用前景;由于磁性纳米粒子有着很大的比表面,容易发生团聚现象,针对如何提高纳米溶胶的稳定性和分散性,引入了纳米粒子的表面修饰技术的概念并介绍了在表面修饰领域取得的一系列的研究进展;DNA 的固定化已广泛用于检测分析、分离纯化,在核酸化学、生物计算、分子遗传学及生物工程的研究中有着不可替代的重要作用。本章节还介绍了DNA 在纳米粒子表面固定化的研究进展及研究展望。
    第二章: 由于磁性Fe3O4纳米粒子有着很大的比表面,磁性偶极间的相互吸引都易导致团聚现象的产生,如何制备出粒径小、分散性好的超细Fe3O4纳米粒子已成为当今倍受关注的研究热点。本章以γ-氨丙基三乙氧基硅烷作分散稳定剂,改善了磁性Fe3O4纳米粒子表面的疏水环境,成功地制备出稳定性好、单分散的磁性Fe3O4/氨基硅烷复合纳米微球,有效地阻止了四氧化三铁纳米粒子团聚的发生。经IR、XRD、TEM、VSM 及UV-Vis 测试结果表明,该种复合微球具备粒径小、粒径分布范围窄(10 ±2 nm)、比饱和磁化强度和超顺磁性等优良性能;经表面改性后,氨基作为功能性基团成功的负载到磁性Fe3O4纳米粒子表面,增强了微球的生物兼容性,因此该种磁性微球在酶的固定、细胞分选、靶向给药等领域有着广泛的应用前景。
    第三章: 采用化学共沉淀法和表面化学修饰的方法制备了以Fe3O4为磁核,氨基硅烷为外壳的超顺磁性硅壳磁纳米粒子。通过氨基硅烷化后,在纳米粒子表面带上氨基碱性基团,在低的pH 值条件下带正电,与DNA 片段中的磷酸根负离子通过静电作用将DNA 固定,构建了一种具超顺磁性的DNA 纳米富集器。应用
Part one: The preparation methods of nanosized magnetite particles such as precipitation and hydrothermal method are summarized, and its widely uses in the fields such as biotechnology was reported, for example, in bio-separation, immunoassays, and DNA immobilization. In this part, surface modification is also introduced as a new nano-technology. the modification methods, modification kinetics and the recent research in surface modifications of nanoparticles was reported.
    Part two: The amino-silane modified magnetite nanoparticles were synthesized by the coprecipitation and surface modification with 3-aminopropyl-triethoxysilane (APTTS). Characterized by TEM and UV-vis, the ultrafine APTTS/Fe3O4 nanospheres had well dispersion and stabilization in aqueous fluids, The superparamagnetic APTTS/Fe3O4 nanospheres with an average diameter of 10 nm were characterized significantly with functional group, as well as a maximized saturation magnetization of 63.54 emu/g, and the optimal surface modification molar ratio of APTTS to Fe3O4 was found to 4:1. Displaying functional group of –NH2, high saturation magnetization, the superparamagnetic APTTS-modified Fe_3O_4 NPs are of significance for magnetic applications in biomedicine.
    Part three: Adsorption of DNA on magnetic nanoparticles was carried out, the interaction between magnetite and DNA and kinetics of the adsorption process were studied. Fe3O4 nanoparticles were prepared by the chemical precipitation method and modified with 3-Aminopropyltriethoxysilane on the surface of magnetite NPs. Characterization of magnetic particles were carried out using transmission electron microscopy and a vibrating sample magnetometer. Fourier-transform infrared spectroscopy was used to confirm the attachment of DNA on magnetic particles. Effect of pH and salt concentrations were investigated on the adsorption process.
    The experiment results show the adsorption of DNA on magnetic particles was effected greatly by the pH and ionic strength. Adsorption kinetics were analyzed by a linear driving force mass-transfer model.
引文
[1]Wang henzhi ,Wu donghui ,Li jianhua. Jiangsu Chemical industry, 2001,29(5)
    [2]Zhu tun ,Wang fuming ,wang xidong Development and application of nanomaterial technology, Beijing ;Chemical Industry Press,2002,96-104
    [3]Qu S C, Yang H B,Ren D W, et al. J Colloid Interface Sci,1999,215:190-192
    [4]Chang cheng, Guo canxiong , Duan xue, Zheng milin. Chinese Journal of Catalysis,2003,24(1)
    [5]Haberko K. Ceramic Intl. 1979,5;148
    [6]Qiu xing-ping Chinese Journal of chemistry 2000,18(6),834-837
    [7]Liu ying ,Wang jianhua ,Gao wei. Functional material ,1992,24(1),20-24
    [8]Correa-Duarte M A, Giersig M, Kotor Net al .LM; Langmuir,1998,14;6430-6435
    [9]F.A.Cotton. Advanced Inorganic Chemistry [M],Bei jing; People Education Press
    [10]Gao wa Chemistry Teaching ,2001,(8),46
    [11]Ding xiaobin ,Sun zonghua ,Wang guoxiang. Chemical Aviso(化学通报),1997,(1),1-6.
    [12]Gupta P K,Hong C T ,Lam C F et al. Int. J. Pham. 1988,43:161
    [13]Ding ming, Sun hong J Magn Mater Devices 2001,32(6)
    [14]Li fengsheng,Luo fusheng,Yang yi, Liu hongying, J Magn Mater Devices,2002,33(6)
    [15]Clark D S,Bailey J E,Yen R et al. Enzyme Microb technol,1984,6;317
    [16]Kharkeviche DA ,A lyautdin R V, Filippor V, I.J. Pharm Pharm Acol,1989.41;286
    [17]Wang zhifei, Li huoshu, Journal of Practical Oncology, 2002,16(1),75-77
    [18]Lubbe AS et al. Cancer Research.1996,56:4686-4693
    [19] Widder KJ. Harino.PA, Marris RM,et al. Eur J Cancer clin oncol,1983;19(1),141-147
    [20]Gupta PK Hong cl Rao Ns, J Pham Sci ,1989;78(4),290-294
    [21] Jagdish S.Dennis HR Joricrosencap; 1990;7(1),67
    [22]Cheng xingbao, Yuan shuguan. J Prac Radiol , 2003;19(7),631-634
    [23]张立德,牟季美。纳米材料和纳米结构。科学出版社,2001
    [24]Pampach R, Haberkc K. Ceramic Powers. Amsterdam: Elsevier Scientific Pub.Company, 1983, 623
    [25]VAN M .C, LEEDEN et al. J Colloid Interface Sci, 1992,152:337
    [26]杨咏来等. 材料导报。1998,12(2):12
    [27]Her R K. The Chemistry of Silica . NewYork: Wiley-Interscience,1979
    [28]沈钟等,化工进展. 1993,(5):44
    [29]Tsutsumi K, Takuhashi H. Colloid £Polymer Sci . 1985,263:506
    [30]谷元. 化工进展. 1994,(1):33
    [31] 施卫贤,杨俊,王亭杰,金涌. 磁性Fe3O4 微粒表面有机改性物理化学学报,2001,17(6):507-510
    [32] 曾桓兴周文运单分子层油酸包覆Fe3O4 的研究应用科学学报.1989,7(1):75-80
    [33] Hao Zeng, Jing Li, Shouheng Sun, Bimagnetic Core/Shell FePt/ Fe3O4 nanoparticles nano letters 2004,4(1):187-190
    [34] 崔亚丽,房喻等.核/壳型Fe3O4/Au 超顺磁性微粒的制备及机理. 中国科学:B辑.2001,31(4):319-324
    [35] 张海永,景晓燕,张密林. 一种新型的纳米功能材料:磁性纳米镁铝水滑石. 无机化学学报,2002,18(2):185
    [36] 黄俊,官建国. 酞菁铜—Fe3O4 纳米复合粒子复合机理及其性能的研究. 硅酸盐学报.2000,28(5).432-436
    [37]Drmanac R, Drmanc S, Strezoska Z, et al. DNA sequence determination by hybridization: a strategy for efficient large-scale sequencing. Science, 1993, 260(11): 1649-1652
    [38]Noble D. DNA sequencing on a chip. Analytical Chemistry, 1995,67(5): 201A
    [39]Mizabekov A D. The use of oligonucleotide hybridization to determine subsequences in a DNA fragment . TIBTECH, 1994,12:27
    [40]Khrapko K R, Lysov Y P, Khorlyn A A, et al. An oligonucleotide hybridzation approach to DNA sequencing . FEBS Lett,1989,256:118-122
    [41]Hacia J G, Brody L C , Chee N S, et al. Detection of heterozygous mutations in BRCA 1 using high density oligonucleotide arrays and two-colour fluorescence analysis. Nat Genet, 1996,14(4):441-447
    [42]Albretsen C, Kalland K H, Haukanes B I, et al. Applications of magnetic beads with covalently attched oligonucleotides in hybridization: isolation and detection of specific measles virus mRNA from a crude cell lysate. Ana Biochem,1990,189(1):40-50
    [43] Lipshutz R J, Morris D, Chee M, et al. Using oligonucleotide probe assays to access genetic diversity, Biotechniques,1995, 19:442-447
    [44]Szymonifka M J, Chapman K T. Magnetic manipulable polymeric supports for solid phase organic synthesis, Tetrahedron Lett,1995,36(10):1597-1600
    [45]Matson R S, Rampal J, Pentoney S L, et al. Biopolymer synthesis on polypropylene supports: oligonucleotide arrays, Anal Biochem, 1995,224(1):110-116
    [46]马文丽,郑文岭. DNA 芯片技术的方法与应用[M]. 广东;广东科技出版社,2002
    [47]Southem E, Mir K, Shehepinov M. Molecular interactions on microarays [J].Nature Genetics, 1999,21 suppl:5-9
    [48]Cheung VG, Morley M, Aguilar F, et al, Making and reading microarrays [J].Nature Genetics, 1999,21 suppl:15-19
    [49]Afanasssiev V, Hanemann V, Wolfl S. Preparation of DNA and protein micro arrays on glass slides coated with an agarose film [J]. Nucleic Acids Research,2000, 28(12):66-73
    [50]Mikhail AP, Eugeny AL, Micharel WR, Attachment of benzaldehyde-modified oligodeoxynucleotide probes to semicarbazide-coated glass [J].Nucleic Acids Research,2001, 29(24): 5090-5098
    [51]Chrisey LA, Lee GU, O Ferrall CE, et al.Covalent attachment of synthetic DNA to self-assembled monolayer films [J]. Nucleic Acids Research, 1995,24(15): 3031-3039
    [52]Dolan PL. WU Yang, Ista LK, et al.Robust and efficient synthetic method for forming DNA micro arrays[J].Nucleic Acids Research,2001,29(21):107-117
    [53]Strother T, Hamers RJ, Smith LM. Covanlent attachment of oligodeoxyribonucleotides to amino-modified Si (001) surfaces[J]. Nucleic Acids Research, 2000,28(18): 3535-3541
    [54]Eric LeProust, ZHANG Hua, YU Pei-lin, et al. Characterization of oligodeoxyribonucleotide synthesis on glass plates [J]. Nucleic Acids Research, 2001,29(10): 2171-2180
    [55]Zammatteo N, Jeanmart L, Hammels S, et al. comparison between different strategies of covalent attachment of DNA to glass surfaces to build DNA micro arrays [J]. Analytical BIOCHEMISTRY,2000,280:143-150
    [56]马文丽,郑文岭,崔东等. 利用瓷片材料制备DNA 微集芯片的研究[J]. 生物化学与生物物理学报,2000,32(3):285-288
    [57]吴清华,马文丽,郑文岭. 不同介质表面寡核苷酸固定化技术的研究. 国外医学生物医学工程分册,2004,27(4):203-206
    [58]Maskos U, Southern EM. Oligonuicleotide hybridizations on glass supports: a novel linker for oligonucleotide synthesis and hybridization properties of oligonucleotides synthesized in Situ[J]. Nucleic Acids research,1992,20(7):1676-1684
    [59]Shchepinov MS, Case-Green SC, Southern EM. Steric factors influencing hybridization of nucleic acids to oligonucleotide arrays[J]. Nucleic Acids Research,1997,25(76):1155-1162
    [60]Gilham P T, The synthesis of polynucleotide-cellloses and their use in the fractionation of polynucleotides. J Am Chem Soc, 1964,86(20):4982-4985
    [61]Kremsky J N, Wocters J L, Dougherty J P, et al. Immobilization of DNA via oligonucleotides containing an aldehyde or carboxylic acid group at the 5’terminus, Nucleic Acids Research,1987, 15(7):2891-2909
    [62]Poonian M S, Schlabach A J, Weibach A. covalent attrachment of nucleic acid to agarose for affinity chromatography Biochemistry, 1971,10(3):424-427
    [63]Nuzzo R G, Fusco F A, Allara D L, Spontaneously organized molecular assemblies(3): preparation and properties of solution adsorbed monolayers of organic disulfides on gold surfaces. J Am Chem Soc ,1987,109(8):2358-2361
    [64]Herne T M, Tarlov M J. Characterization of DNA probes immobilized on gold surfaces. J Am Chem Soc, 1997,119(38): 8916-8920
    [65]Nikura K, Nagata K, Okahata Y. Quantitative detection of protein binding onto DNA by using a quartz crystal mircrobalance . Chemistry Letters, 1996:863-864
    [66]Thiel A J. Frutos A G, Jordan C E, et al. In situ surface plasmon resonance imaging detection of DNA hybridization to oligonucleotide arrays on gold surfaces . Anal Chem,1997,69:4948-4956
    [67]Jordan C E, Frutos A G, Thiel A J, et al. Surface plasmon resonance imaging measure ments of DNA hybridization adsorption and streptavidin/DNA multiplayer formation at chemically modified gold surfaces. Anal Chem, 1997,69:4939-4947
    [68]Abel A P. Weller M G, Duveneck G L, et al. Fiber-optic evanescent wave biosensor for detection of oligonucleotides. Anal Chem, 1996,68(17):2905-2912
    [69]Okahata Y, Kawase M, Niikura K, et al. Kinetic measurements of DNA hybridization on an oligonuclectide-immobilized 27-MHz quarz crystal microbalance. Anal Chem,1998,70:1288-1296
    [70]Caruso F, Rodda E, Fulong D N, et al. Quartz crystal microbalance study of DNA immobilization and hybridization for nucleic acid sensor development. Anal Chem,1997,69: 2043-2049
    [71]Henke L, Piunno P A E, McClure A C, et al. covalent immobilization of single-stranded DNA onto optical fibers using various linkers. Anal Chim Acta,1997,344:201-213
    [72] 林红霞. 超顺磁性铁氧体纳米微粒造影剂的研究沈阳药科大学硕士论文2001 年6 月
    [73] 周公度,段连运著结构化学基础, 北京大学出版社(第二版)1995:395
    [74] J. M. Petez, F. J. Simeone, Y. Saski, L. Josephson, and R. Weissleder, J. Am. Chem. Soc., 2003,125,10192.
    [75] R. Weissleder, A. Bogdanov, E. A. Neuwelt, and M. Papisov, Adv. Drug Delivery Rev., 1995, 16, 321.
    [76]Xing-Can Shen, Xiu-Zhong Fang, et al. Synthesis and characterization of 3-Aminopropyl-triethoxysaline-modified superparamagnetic magnetite nanoparticles. Chemitry Letters, 2004,33 (11) 1468-1469.
    [77]Abudiab T, Beitle R R. Preparation of magnetic immobilized meta affinity separation media and its use in the isolation of proteins. J Chromatogr A, 1998,795:211-217
    [78]Josephson L, et al. Magnetic particles for use in separations. US Patent, 4672040, 1987-06-09
    [79]H-H.Yang,S-Q.Zhang,X-L Chen,Z-X Zhang,J-G Xu and X-R Wang, Anal .Chem., 76,1316 (2004)
    [80]D.K.Kim et al, Surface modification of superparamagnetic nanoparticles for in-vivo bio-medical applications, Mat.Res.Soc.Symp.Proc. 2002,704,1124.
    [81]A.Jordan, R.Scholz,P. Wust, H.Schbirra, T.Schiestel, H. Schmidt, R.Felix, J.Magn.Magn.Mater, 1999,194, 185.
    [82] Hong Xia, BaiYu-bai et al, etal. Chem.J.ChineseUniversities (高等学校化学学报) [J],2003,24(7):1293—1295
    [83]Gupta PK, Hung CT. Magnetically controlled targeted micro-carrier systems. Life Sci 1989;44:175-186
    [84]Lifen Shen,Paul E.Laibins, and T.Alan Hatton, Langmuir, vol 15,No 2 (1999)
    [85]Ryosuke Matsuno et al, Chem.Mater.2003,15,3-5
    [86]Xingcan Shen,Xiwen He, Hong Liang, Chinese Journal of Analytical Chemistry(分析化学) ,2003, 31: 880-885
    [87] Mikhaylova, D. K. Kim, N. Bobrysheva, M. Osmolowsky, T. Tsakalakos, and M. Muhammed, Langmuir, 2004, 20, 2472.
    [88] A. Harris, J. D. Goff, A. Y. Carmichael, J. S. Riffle, J. J. Harburn, T. G. St. Pierre, and M. Saunders, Chem. Mater., 2003,15, 1367.
    [89]Hao Zeng et al, Bimagnetic Core/Shell FePt/Fe3O4 Nanoparticles, Nano Letters,vol 4,No.1 187-190
    [90] Gruttner C,Teller J et all,Scientific and Clinical Applications of Magnetic carriers[M],New York:Plenum Press,1997,53-67
    [91]Physical Chemistry(物理化学), Advanced Education Press(高等教育出版社), Bei Jing,1990
    [92]Martin C R, Mitchell D T. Analytical Chemistry News & Features[J], 1998, 70:322A-327A
    [93]Sonti S V, Bose A, et al. J.Colloid.Interface sci.[J],1995, 1,70:575-585
    [94]何哓哓,王柯敏等. 基于生物荧光纳米颗粒的新型荧光标记方法及其在细胞识别中的应用. 科学通报[J], 2001,46(23):1962-1965
    [95] He X. X.,Wang K. M .,TanW. H. et a l.. J. Nanosci. Nanotech.[J],2002, 2: 317-320
    [96] 何晓晓,王柯敏等: 超顺磁性DNA纳米富集器应用于痕量寡聚核普酸的富集. 高等学校化学学报[J], 2003,1:40-42
    [97]B. Sinclair, Scientist 12 (1998) 17.
    [98] I. Safaryk, M. Safarykova, J. Chromatogr. 1999,33, B 722.
    [99]Yoza, Brandon, Matsumoto, Mitsufumi, et al. DNA extraction using modified bacterial magnetic particles in the presence of amino silane compound. Journal of Biotechnology. 2002, 3:217-224
    [100]Bruce, Ian J, Taylor, James, et al. Synthesis, characterization and application of silica-magnetite nanocomposites. J Magnetism.Magnetic.Materials,2004,286:145-160
    [101]Taylor, James I, Hurst, Carolyn D, et al. Application of magnetite and silica–magnetite composites to the isolation of genomic DNA. Journal of Chromatography A,2000,890:159-166
    [102]Mornet S, Vekris A, Portier J, et al. DNA-magnetite nanocomposite materials. Materials Letters, 2000,3(42):183-188
    [103]Davis, Martin J, Taylor, James I, et al. Isolation of Plasmid DNA Using Magnetite as a Solid-Phase Adsorbent. Analytical Biochemistry, 1998,262:92-94
    [104]Elizabeth Bertani L, Huang, Jerry S, et al. Evidence for two types of subunits in the bacterioferritin of Magnetospirillum magnetotacticum. Gene, 1997,201:31-36
    [105]Cheng, Guifang; Zhao, Jie; et al. A sensitive DNA electrochemical biosensor based on magnetite with a glassy carbon electrode modified by muti-walled carbon nanotubes in polypyrrole. Analytica Chimica Acta, 2005,1(533):11-16
    [106]Twardowski J. , Anzenbacher P. Ram an and IR Spectroscopy in Biology and Biochemistry[ M},New York: E His Horwood Limited, 1994
    [107] James M.B.,MichaelA. W.,George J. T. Jr.. Biochemistry[J],1991,30: 5955-5963
    [108]董丽琴,周剑章等. 自组装DNA与[Co(phen)3 ]2+/3+相互作用的表面增强拉曼光谱法研究.高等学校化学学报[J], 2003,2:315-319
    [109]Lin N P, Deen . W M. J. Colloid. Interface. Sci 1992, 153(2): 483-492
    [110]Cha W, Beissinger R L. J. Colloid. Interface. Sci 1996, 177: 666-674