近年來伴隨著奈米科技的發展，磁性奈米材料廣泛的應用於生物
醫學技術上。由於其獨特的超順磁特性，在外加磁場下，可以作為體
內傳遞藥物的載體，並配合熱治療 (hyperthermia) 的技術，能夠有效
殺死癌細胞，在醫學上相當具有研究價值。
本研究利用二氧化矽包覆磁性奈米粒子，並進一步在其表面修飾
β-環狀糊精，探討奈米粒子於熱治療上的效應；最後利用環狀糊精能
與藥物形成複合物的特性，觀察披落卡藥物 (piroxicam) 於此奈米複
合載體上的釋放行為。本研究以共沉澱法製備磁性奈米氧化鐵粒子，
以X-ray 繞射儀 (X-ray diffractometer, XRD) 鑑定其結構為Fe3O4 之
晶相，並以檸檬酸修飾粒子表面，利用傅立葉紅外線光譜儀 (Fourier
Transform Infrared Spectrophotometer, FT-IR) 及熱重分析儀
(Thermogravimetric Analysis, TGA) 鑑定已成功修飾；繼而利用穿透
式電子顯微鏡 (Transmission Electron Microscope , TEM) 影像分析及
XRD 平均微晶尺寸的估算，得知經由檸檬酸修飾前後的奈米粒子尺
寸分別為9.5 nm、10.4 nm 及8.9 nm、9.1 nm，得知經過改質後的粒
子尺寸要比修飾前略小；在磁性分析上，從磁滯曲線可以得知經過檸
檬酸修飾前後，磁性奈米粒子之飽和磁化量分別為71.5 emu/g 及64.0
emu/g。利用二氧化矽包覆後的磁性奈米氧化鐵，經由XRD 及FT-IR
確定氧化鐵的結構，並得知磁流體與tetraethoxysilane (TEOS) 體積比
為0.5 ml : 0.5 ml 時具有較佳的粒子形貌；透過磁滯曲線可以觀察到
TEOS 的加量影響Fe3O4@silica 奈米粒子的飽和磁化量。
以 β- 環狀糊精修飾Fe3O4@silica 奈米粒子， 首先利用
3-isocyanatopropyltriethoxysilane (3-ICPTES) 與 β-環狀糊精產生共價
鍵結 (β-CD-silane)，藉由FTIR 及核磁共振光譜儀 (Nuclear Magnetic
Resonance, NMR) 證實已存在胺基甲酸酯的結構並確定矽醇氧基端
並未水解；之後將 β-CD-silane 修飾於Fe3O4@silica 奈米粒子表面，
藉由FT-IR、TGA 及能量散佈光譜儀 (Energy Dispersive Spectrometer,
EDS) 證實粒子表面確實有 β-環狀糊精之存在；最後從TEM 得知，
奈米粒子經由 β-環狀糊精後會產生粒子聚集的現象。
磁性奈米粒子熱效應的探討上，首先得知以檸檬酸修飾之磁性奈
米氧化鐵 (citric acid modified magnetic nanoparticle, CNM) 在施加磁
場30 min 內，能夠使溶液達到42 oC 以上的溫度。經由二氧化矽包覆
後，Fe3O4@silica 奈米粒子升溫效應明顯下降，由實驗得知溫度的變
化量與TEOS 的添加量有關。在藥物的包覆上，可以發現 β-CD-silane
與piroxicam 形成複合物的條件會影響藥物最後的包覆效率；藥物與
載體所形成的複合物 (piroxicam -SNM-β-CD) 於磷酸鹽水溶液下進
行藥物釋放，可以得知藥物釋放的比例為21.3 %。

Magnetic nanoparticles extensivily apply to biologically medical
technology following the development of nanotechnology. Magnetic
nanoparticles can be used as a drug carrier due to their size-dependent
superparamagnetism. Magnetic nanoparticles also can inhibit the cancer
cell by hyperthermia technique.
In the study, by the silica was coated onto the magnetic
nanoparticles which were stabilized by citric acid. The surface of the
nanoparticles was further modified with β-cyclodextrin. The thermal
effect of the magnetic nanoparticles under applied magnetic filed was
also investigated. The release behavior of piroxicam were carried on the
SNM-β-CD surface was also studied. In this work, magnetic
nanoparticles were synthesized by co-precipitation method. The
modification by citric acid (CNM) was confirmed by FT-IR and TGA.
The sizes of Fe3O4 and CNM were estimated to be around 10.4 nm and
9.1 nm from TEM photo. The average crystalline sizes were about 9.5 nm
and 8.9 nm, respectively. SQUID results indicated that saturation
magnetization of Fe3O4 and CNM was 71.5 emu/g and 64.0 emu/g. FT-IR
and XRD further confirmed the Fe3O4 structure of magnetic nanoparticles
coated by silica (Fe3O4@silica). A volume ratio of CNM/TEOS of 0.5 ml :
0.5 ml could achieve a better shape of Fe3O4@silica.
To further coat Fe3O4@silica nanoparticle by β-cyclodextrin, the
β-cyclodextrin and 3-isocyanatopropyltriethoxysilane (3-ICPTES)
(β-CD-silane) were bound together. FT-IR and NMR confirmed the
urethane and silane structures on β-CD-silane. Further, Fe3O4@silica
nanoparticle was modify by β-CD-silane. FT-IR, TGA and EDS was used
to confirm the presence of β-cyclodextrin.
CNM could raise the temperature from 37 oC to 42 oC under applied
magnetic filed. The thermal effect of Fe3O4@silica could remarkably
decrease. The efficiency (η) of the drug carrier was dependent on thecondition of piroxicam and β-CD-silane complex. The drug release
percentage of piroxicam-SNM-β-CD complex could be achieved at
current stage was 21.3 %.

1.何鎮揚, 陳雅玲, 廖家榮, 奈米科技交響曲化學篇, 2004

2.顧寧, 付德剛, 張海黔, 奈米技術與應用, 2003

3.D.L. Leslie-Pelecky, R.D. Rieke, Magnetic Properties of Nanostructured Materials, Chemistry of Materials, 8, 1770-1783, 1996

4.R. Asmatulu, M.A. Zalich, R.O. Claus, J.S. Riffle, Synthesis, characterization and targeting of biodegradable magnetic nanocomposite particles by external magnetic fields, Journal of Magnetism and Magnetic Materials, 292, 108-119, 2005

5.L. Fu, V.P. Dravid, D.L. Johnson, Self-assembled (SA) bilayer molecular coating on magnetic nanoparticles, Applied Surface Science, 181, 173-178, 2001

6.C.J. O’Connor, C.T. Seip, E.E. Carpenter, S. Li, V.T. John, Synthesis and reactivity of nanophase ferrites in reverse micellar solutions, Nanostructured Materials, 12, 65-70, 1999

7.D. Thapa, V.R. Palkar, M.B. Kurup, S.K. Malik, Properties of magnetite nanoparticles synthesized through a novel chemical route, Materials Letters, 58, 2692-2694, 2004

8.R. Massart, Preparation of aqueous magnetic liquids in alkaline and acidic media, IEEE Transactions on Magnetics, 17, 1247-1248, 1981

9.C.L. Lin, C.F. Lee, W.Y. Chiu, Preparation and properties of poly(acrylic acid) oligomer stabilized superparamagnetic ferrofluid, Journal of Colloid and Interface Science, 291, 411-420, 2005

10.S. Sun, H. Zeng, Size-Controlled Synthesis of Magnetite Nanoparticles, Journal of the American Chemical Society, 124, 8204-8205, 2002

11.S. Sun, H. Zeng, D.B. Robinson, S. Raoux, P.M. Rice, Monodisperse MFe2O4 (M = Fe, Co, Mn) Nanoparticles, Journal of the American Chemical Society, 126, 273-279, 2004

12.K. Woo, J. Hong, S. Choi, H.W. Lee, J.P. Ahn, C.S. Kim, S.W. Lee, Easy synthesis and magnetic properties of iron oxide nanoparticles, Chemistry of materials, 16, 2814-2818, 2004

13.I.W. Hamley, Nanotechnology with Soft Materials, Angewandte Chemie International Edition, 42, 1692-1712, 2003

14.T. Tepper, F. Ilievski, C.A. Ross, T.R. Zaman, R.J. Ram, S.Y. Sung, B.J.H. Stadler, Magneto-optical properties of iron oxide films, Journal of Applied Physics, 93(10), 6948-6950, 2003

15.L. Shen, P.E. Laibinis, T.A. Hatton, Bilayer surfactant stabilized magnetic fluids: synthesis and interactions at interfaces, Langmuir, 15, 447-453, 1999

16.Y. Sahoo, A. Goodarzi, M.T. Swihart, T.Y. Ohulchanskyy, N. Kaur, E.P. Furlani, P.N. Prasad, Aqueous ferrofluid of magnetite nanoparticles: fluorescence labeling and magnetophoretic control, The Journal of Physical Chemistry B, 109, 3879-3885, 2005

17.H. Pardoe, W. Chua-anusorn, T.G.St. Pierre, J. Dobson, Structural and magnetic properties of nanoscale iron oxide particles synthesized in the presence of dextran or polyvinyl alcohol, Journal of Magnetism and Magnetic Materials, 225, 41-16, 2001

18.M.C. Bautista, O. Bomati-Miguel, M.P. Morales, C.J. Serna, S. Veintemillas-Verdaguer, Surface characterisation of dextran-coated iron oxide nanoparticles prepared by laser pyrolysis and coprecipitation, Journal of Magnetism and Magnetic Materials, 293, 20-27, 2005

19.H.Y. Acar, R.S. Garaas, F. Syud, P. Bonitatebus, A.M. Kulkarni, Superparamagnetic nanoparticles stabilized by polymerized PEGylated coatings, Journal of Magnetism and Magnetic Materials, 293, 1-7, 2005

20.T. Yang, C. Shen, Z. Li, H. Gao, Highly ordered self-assembly with large area of Fe3O4 nanoparticles and the magnetic properties, The Journal of Physical Chemistry B, 109, 23233-23236, 2005

21.B. Zelbi, A.S. Susha, G.B. Sukhorukov, A.L. Rogach, W.J. Parak, Magnetic targeting and cellular uptake of polymer microcapsules simultaneously functionalized with magnetic and luminescent nanocrystals, Langmuir, 21, 4262-4265, 2005

22.A.K. Gupta, M. Gupta, Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications, Biomaterials, 26, 3995-4021, 2005

23.A.K. Gupta, A.S.G. Curtis, Lactoferrin and ceruloplasmin derivatized superparamagnetic iron oxide nanoparticles for targeting cell surface receptors, Biomaterials, 25, 3029-3040, 2004

24.A.K. Gupta, M. Gupta, A. Curtis, Receptor-mediated targeting of magnetic nanoparticles using insulin as a surface ligand to prevent endocytosis, IEEE Transactions on Nanobioscience, 2, 255-261, 2003

25.J.W.M. Bulte, T. Douglas, B. Witwer, S.C. Zhang, E. Strable, B.K. Lewis, Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells, Nature Biotechnology, 19, 1141-1147, 2001

26.T. Neuberger, B. Schőpf, H. Hofmann, M. Hofmann, B. von Rechenberg, Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system, Journal of Magnetism and Magnetic Materials, 293, 483-496, 2005

27.M. Zhao, D.A. Beauregard, L. Loizou, B. Davletov, K.M. Brindle, Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent, Nature Medicine, 7, 1241-1244, 2001

28.K.L. Ang, S. Venkatraman, R.V. Ramanujan, Magnetic PNIPA hydrogels for hyperthermia applications in cancer therapy, Materials Science and Engineering C, 27, 347-351, 2007

29.M. Shinkai, M. Yanase, H. Honda, T. Wakabayashi, J. Yoshida, T. Kobayashi, Intracellular hyperthermia for cancer using magnetite cationic liposomes: in vitro study, Japanese Journal of Cancer Research, 87, 1179-1183, 1996

30.F. Matsuoka, M. Shinkai, H. Honda, T. Kubo, T. Sugita, Hyperthermia using magnetite cationic liposomes for hamster osteosarcoma, Biomagnetic Research and Technology, 2(3), 1-6, 2004

31.M. Shinkai, M. Yanase, H. Honda, T. Wakabayashi, J. Yoshida, T. Kobayashi, Intracellular hyperthermia for cancer using magnetite cationic liposomes: ex vivo study, Japanese Journal of Cancer Research, 88, 630-632, 1997

32.P. Walde, Preparation of Vesicles (Liposomes), Encyclopedia of Nanoscience and Nanotechnology, 9, 43-79, 2004

33.F.M. Rocha, S.C. de Pinho, R.L. Zollner, M.H.A. Santana, Preparation and characterization of affinity magnetoliposomes useful for the detection of antiphospholipid antibodies, Journal of Magnetism and Magnetic Materials, 225, 101-108, 2001

34.J. Giri, S.G. Thakuta, J. Bellare, A.K. Nigam, D. Bahadur, Preparation and characterization of phospholipid stabilized uniform sized magnetite nanoparticles, Journal of Magnetism and Magnetic Materials, 293, 62-68, 2005

35.S. Lesieur, M.S. Martina, J.P. Fortin, C. Ménager, O. Clément, Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging, Journal of the American Chemical Society, 127, 10676-10685, 2005

36.M. Koneracká, P. Kopčansky, P. Sosa, Milan Timko, Interliposomal transfer of crystal violet dye from DPPC liposomes to magnetoliposomes, Journal of Magnetism and Magnetic Materials, 293, 271-276, 2005

37.Z. Ma, H. Liu, Synthesis and surface modification of magnetic particles for application in biotechnology and biomedicine, China Particuology, 5, 1-10, 2007

38.E.B. Denkbaş, E. Kilicay, C. Birlikseven, E. Őztűrk, Magnetic chitosan microspheres: preparation and characterization, Reactive & Functional Polymers, 50, 225-232, 2002

39.S. Santra, R. Tapec, N. Theodoropoulou, J. Dobson, A. Hebard, W. Tan, Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion: the effect of nonionic surfactants, Langmuir, 17, 2900-2906, 2001

40.Y.H. Deng, C.C. Wang, J.H. Hu, W.L. Yang, S.K. Fu, Investigation of formation of silica-coated magnetite nanoparticles via sol–gel approach, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 262, 87-93, 2005

41.V.S. Salgueiriño-Maceira, M.A. Correa-Duarte, M. Spasova, M. Farle, Composite silica spheres with magnetic and luminescent functionalities, Advanced Functional Materials, 16, 509-514, 2006

42.T. Loftsson, D. Duchêne, Cyclodextrins and their pharmaceutical applications, International Journal of Pharmaceutics, 329, 1-11, 2007

43.M.E. Davis, M.E. Brewster, Cyclodextrin-based pharmaceutics: past, present and future, Nature Review, 3, 1023-1035, 2004

44.E.M. Martin Dell Valle, Cyclodextrins and their uses: a review, Process Biochemistry, 39, 1033-1046, 2004

45.M.E.A. Dalmora, A.G. Oliveira, Inclusion complex of piroxicam with β-cyclodextrin and incorporation in hexadecyltrimethylammonium bromide based microemulsion, 184, 157-164, 1999

46.T. Srichana, R. Suedee, W. Reanmongkol, Cyclodextrin as a potential drug carrier in salbutamol dry powder aerosols: the in-vitro deposition and toxicity studies of the complexes, Respiratory Medicine, 95, 513-519, 2001

47.K. Uekama, F. Hirayama, T. Irie, Cyclodextrin Drug Carrier Systems, Chemical Reviews, 98, 2045-2076, 1998

48.F. Hirayama, K. Uekama, Cyclodextrin-based controlled drug release system, Advanced Drug Delivery Reviews, 36, 125-141, 1999

49.A.K. Upadhyay, S. Singh, R.R. Chhipa, M.V. Vijayakumar, A.K. Ajay, M.K. Bhat, Methyl-β-cyclodextrin enhances the susceptibility of human breast cancer cells to carboplatin and 5-fluorouracil: Involvement of Akt, NF-κB and Bcl-2, Toxicology and Applied Pharmacology, 216, 177-185, 2006

50.S.S. Braga, M.P.M. Marques, J.B. Sousa, M. Pillinger, J.J.C. Teixeira-Dias, I.S. Goncalves, Inclusion of molybdenocene dichloride (Cp2MoCl2) in 2-hydroxypropyl- and trimethyl-β-cyclodextrin: Structural and biological properties, 690, 2905-2912, 2005

51.M. Fermeglia, M. Ferrone, A. Lodi, S. Pricl, Host–guest inclusion complexes between anticancer drugs and β-cyclodextrin: computational studies, Carbohydrate Polymer, 53, 15-44, 2003

52.T. Cserháti, E. Forgács, Use of spectral mapping technique for the evaluation of the formation of inclusion complexes between anticancer drugs and cyclodextrin derivatives, Chemometrics and Intelligent Laboratory Systems, 40, 93-100, 1998

53.P.Y. Grosse, F. Bressolle, F. Pinguet, In Vitro Modulation of Doxorubicin and Docetaxel Antitumoral Activity by Methyl-β-cyclodextrin, European Journal of Cancer, 34, 168-174, 1998

54.S. Rozou, A. Voulgari, E. Antoniadou-Vyza, The effect of pH dependent molecular conformation and dimerization phenomena of piroxicam on the drug: cyclodextrin complex stoichiometry and its chromatographic behaviour A new specific HPLC method for piroxicam:cyclodextrin formulations, European Journal of Pharmaceutical Sciences, 21, 661-669, 2004

55.M. Jug, M. Bećirević-Laćan, Influence of hydroxypropyl-β-cyclodextrin complexation on piroxicam release from buccoadhesive tablets, European Journal of Pharmaceutical Sciences, 21, 251-260, 2004

56.G. Xiliang, Y. Yu, Z. Guoyan, Z. Guomei, C. Jianbin, S. Shaomin, Study on inclusion interaction of piroxicam with β-cyclodextrin derivatives, Spectrochimica Acta Part A, 59, 3379-3386, 2003

57.C. Zheng, A. Lin, X. Zhen, M. Feng, J. Huang, H. Zhan, Structural and textural evolution of dimethyl-modified silica xerogels, Materials Letters, 61, 2927-2930, 2007

58.K. Liu, Q. Feng, Y. Yang, G. Zhang, L. Ou, Y. Lu, Preparation and characterization of amorphous silica nanowires from natural chrysotile, Journal of Non-Crystalline Solids, 353, 1534-1539, 2007

59.Y. Sun, L. Duan, Z. Guo, Y. DuanMu, M. Ma, L. Xu, Y. Zhang, N. Gu, An improved way to prepare superparamagnetic magnetite-silica core-shell nanoparticles for possible biological application, Journal of Magnetism and Magnetic Materials, 285, 65-70, 2005

60.T.E. Vasquez, J.M. Bergset, M.B. Fierman, A. Nelson, J. Roth, S.I. Khan, D.J. O’Leary, Using equilibrium isotope effects to detect intramolecular OH/OH hydrogen bonds, structural and solvent effects, Journal of the American Chemical Society, 124, 2931-2938

61.N.R. Pedersen, J.B. Kristensen, G. Bauw, B.J. Ravoo, R. Darcy, K.L. Larsen, L.H. Pedersen, Thermolysin catalyses the synthesis of cyclodextrin esters in DMSO, Tetrahedron: Asymmetry, 16, 615-622, 2005

62.M.A. Zulfikar, A.W. Mohammad, Synthesis and characterization of poly(methyl methacrylate)/SiO2 hybrid membrane, Materials Science and Engineering A, 452, 422-426, 2007

63.M. Shinkai, M. Yanase, M. Suzuki, H. Honda, T. Wakabayashi, J. Yoshida, T. Kobayashi, Intracellular hyperthermia for cancer using magnetite cationic liposomes, Journal of Magnetism and Magnetic Materials, 194, 176-184, 1999

64.黄佳琪, 以磷脂質修飾之奈米顆粒之製備與性質鑑定, 2006

65.Y.K. Lee, M.H. Lee, I.B. Shim, D.H. Kim, S.H. Lee, K.H. Im, K.N. Kim, K.M. Kim, Surface-modified magnetite nanoparticles for hyperthermia: Preparation, characterization, and cytotoxicity studies, Current Applied Physics, 6S1, e242–e246, 2006