人類文明進步，日常生活中的致癌物質不斷增加，如工業化學物質、農藥、食品添加物等。使人類罹患癌症機率不斷上升，癌症以成為國人十大死因之首，同時也是先進國家十大死因之ㄧ。幾丁聚醣具有良好生物相容性和生物降解性，在自然界中含量僅次於纖維素，結構上近似於胺基葡聚醣，且因成本低廉，來源穩定，本研究將以幾丁聚醣做為材料。

本研究利用利用共沉澱法合成四氧化三鐵粒子，由於凡得瓦力作用，使磁性粒子產生嚴重聚集，降低實用性。我們利用幾丁聚醣胺基與丙烯酸進行Michael addition反應，使其帶有羧酸官能基後與四氧化三鐵粒子產生化學鍵結，利用磁性粒子表面鍵結高分子空間位阻效應增加粒子分散性，且因粒子表面包覆一層改質幾丁聚醣高分子，將增加磁性粒子生物相容性。然後將改質與未改質四氧化三鐵粒子加入幾丁聚醣與聚乙二醇高分子溶液均勻混和，利用電紡絲技術製備出磁性奈米纖維與磁性纖維薄膜，並透過SQUID、XRD、SEM、TEM等儀器去觀察磁性纖維形態與分析纖維磁學特性。

我們量產磁性纖維薄膜並置於高週波線圈內，去模擬熱療法加熱環境與觀察升高溫度。結果發現在固定高週波磁場下，含有改質四氧化三鐵粒子纖維薄膜，其升高溫度與磁性粒子添加量和每毫升水含有磁性纖維克數有關。而在相同磁場下，含有未改質四氧化三鐵粒子纖維薄膜，其升高溫度同樣與每毫升水含有纖維克數有關，但其升高溫度卻與磁性粒子添加量無明顯關係存在而與粒子在纖維內聚集情形有關。

癌細胞因缺少正常血管組織，無法藉擴張運動把過多熱量帶走，故熱敏溫度較低，本實驗製備含有改質與未改質四氧化三鐵粒子磁性薄膜，其上升溫度可達40到45℃，可有效用於癌症過熱治療(Hyperthermia in Cancer)。

Cancer has been ranked as the #1 leading cause of death in Taiwan since 1982, according to the Department of Health (DOH, R.O.C.). The development of new cancer treatment is an important component of biomedical research today because there are still many types of cancer that have extremely poor therapy success, such as glioblastoma and pancreatic cancer. In our laboratory, we aim to invent advanced biomaterials and treatment modalities for cancer application.

Due to the inherent superparamagnetic properties, magnetic nanoparticles have been studied for various applications including magnetic resonance imaging, drug and gene targeting and hyperthermia. Electrospinning is recognized as an efficient method for the fabrication of nanofibers. Nanofibers have amazing characteristics such like large surface area-to-volume ratio and high porosity; therefore, nanofibers can be promising for many biomedical applications. Chitosan is produced by deacetylation of chitin and it’s a linear polysaccharide. Due to its excellent biocompatibility, biodegradability and low toxicity, chitosan has been explored for further development in biomedical applications.

In this research, we used co-precipitation method to produce magnetic particles but the aggregation of particles, due to Van der Waals and dipole-dipole interactions, had limited its applications. In order to prepare well dispersed magnetic nanoparticles, the nanoparticles were coated with a biocompatible chitosan derivative, in which chitosan was reacted with acrylic acid to form a water-soluble polymer with carboxyl groups (M-CS). This chitosan derivative can directly bond to magnetic particles by chemisorption via carboxylic groups. Then these magnetite particles had increase dispersion stability and biocompatibility.

Surface coated magnetite particles and virgin magnetite particles were added respectively to the chitosan and PEO polymer solution for the preparation of electrospinning magnetic nanofibers. Magnetic nanofibers and film with modified and pure magnetite particles were generated by electrospinning technique. The material characteristics of these products were characterized by XRD、SEM、TEM and SQUID. In addition, the heating characteristics were evaluated by constant external alternating magnetic field.

Under a constant external alternating magnetic field, we have noted that the temperature was increased proportional to the amount of magnetic fibers within the solution. In addition, for the magnetic nanoparticles coated with chitosan derivative, the temperature was increased with the amount of magnetic nanoparticles added. In contrast, for the uncoated nanoparticles, the temperature increased was not correlated to the amount of nanoparticles added. This is likely due to the aggregation of noncoated magnetic nanoparticles.

It was noted that the temperature of nanocomposites that were formed by the magnetic particles and chitosan electrospinning nanofibers can be heated up to higher than 40C under alternating magnetic field. This implicated these nanocomposites formed by nanomagnetic nanoparticles and nanofibers can be of great potential for hyperthermia treatment for cancer.

1.馬振基，奈米材料科技原理與應用，全華科技圖書股份有限公司.
2.林中魁 林鴻明，奈米科技應用與展望，工業材料179期，84-91，2001.
3.王思婷，具核殼結構的磁性微脂粒之熱效應研究，國立成功大學化學工程研究所碩士論文，2008.
4.吳其章，奈米纖維應用領域分析，紡織產業綜合研究所，1-4，2009.
5.Homayoni H, Ravandi SAH, Valizadeh M. Electrospinning of chitosan nanofibers:Processing optimization. Carbohydrate Polymers,77(3):656-661, 2009.
6.Huang Z. A review on polymer nanofibers by electrospinning and their applications in nanocomposites. Composites Science and Technology,63(15): 2223-2253,2003.
7.Cooley JF. U.S.: 692,631; 1902.
8.Morton WJ. U.S.: 0,705,691; 1902.
9.Formhals A. U.S.: 2,349,950; 1944.
10.Formhals A. U.S.: 1,975,504; 1934.
11.Teo WE, Ramakrishna S. A review on electrospinning design and nanofibre assemblies. Nanotechnology,17(14):R89-R106,2006.
12.Taylor G. Electrically driven jets. Proceedings of the Royal Society of London Series a-Mathematical and Physical Sciences,313(1515):453,1969.
13.Rinaudo M. Chitin and chitosan:Properties and applications. Progress in Polymer Science,31(7):603-632,2006.
14.Kumar M. A review of chitin and chitosan applications. Reactive & Functional Polymers,46(1):1-27,2000.
15.Pillai CKS, Paul W, Sharma CP. Chitin and chitosan polymers: chemistry, solubility and fiber formation. Progress in Polymer Science,34(7):641-678, 2009.
16.Sashiwa H. Chemically modified chitin and chitosan as biomaterials. Progress in Polymer Science,29(9):887-908,2004.
17.Schiffman JD, Schauer CL. A review: Electrospinning of biopolymer nanofibers and their applications. Polymer Reviews,48(2):317-352,2008.
18.Harris JM, Struck EC, Case MG, Paley MS, Vanalstine JM, Brooks DE. Synthesis and characterization of poly(ethylene glycol) derivatives. Journal of Polymer Science Part a-Polymer Chemistry,22(2):341-352,1984.
19.Sawhney AS, Pathak CP, Hubbell JA. Bioerodible hydrogels based on photopolymerized poly(ethylene glycol)-co-poly(alpha-hydroxy acid) diacrylate macromers. Macromolecules,26(4):581-587,1993.
20.Meenach SA, Hilt JZ, Anderson KW. Poly(ethylene glycol)-based magnetic hydrogel nanocomposites for hyperthermia cancer therapy. Acta Biomaterialia, 6(3):1039-1046,2010.
21.Satarkar NS, Zach Hilt J. Hydrogel nanocomposites as remote-controlled biomaterials. Acta Biomaterialia,4(1):11-16,2008.
22.Li LL, Tang FQ, Liu HY, Liu TL, Hao NJ, Chen D, Teng X, He JQ. In vivo delivery of silica nanorattle encapsulated docetaxel for liver cancer therapy with low toxicity and high efficacy. Acs Nano,4(11):6874-6882,2010.
23.Sun SH, Zeng H, Robinson DB, Raoux S, Rice PM, Wang SX, Li GX. Monodisperse MFe2O4 (M = Fe, Co, Mn) nanoparticles. Journal of the American Chemical Society,126(1):273-279 2004.
24.Pankhurst QA, Connolly J, Jones SK, Dobson J. Applications of magnetic nanoparticles in biomedicine. Journal of Physics D-Applied Physics, 36(13):R167-R181,2003.
25.Wang X, Zhuang J, Peng Q, Li Y. A general strategy for nanocrystal synthesis. Nature,437(7055):121-124,2005.
26.Deng H, Li X, Peng Q, Wang X, Chen J, Li Y. Monodisperse magnetic single-crystal ferrite microspheres. Angewandte Chemie International Edition,44(18):2782-2785,2005.
27.Guo L, Huang Q, Li X-y, Yang S. Iron nanoparticles: synthesis and applications in surface enhanced raman scattering and electrocatalysis. Physical Chemistry Chemical Physics,3(9):1661-1665,2001.
28.Li F. Microemulsion and solution approaches to nanoparticle iron production for degradation of trichloroethylene. Colloids and Surfaces A: Physicochemical and Engineering Aspects,223(1-3):103-112,2003.
29.Smith TW, Wychick D. Colloidal iron dispersions prepared via the polymer-catalyzed decomposition of iron pentacarbonyl. Journal of Physical Chemistry,84(12):1621-1629,1980.
30.Kang YS, Risbud S, Rabolt JF, Stroeve P. Synthesis and characterization of nanometer-size Fe3O4 and gamma-Fe2O3 particles. Chemistry of Materials,
8(9):2209,1996.
31.劉陽橋 高濂 孫靜，奈米粉體的分散及表面改性，五南圖書出版公司，2005.
32.Deitzel JM, Kleinmeyer J, Harris D, Tan NCB. The effect of processing variables on the morphology of electrospun nanofibers and textiles. Polymer , 42(1):261-272,2001.
33.Demir MM, Yilgor I, Yilgor E, Erman B: Electrospinning of polyurethane fibers. Polymer,43(11):3303-3309,2002.
34.Fong H, Chun I, Reneker DH. Beaded nanofibers formed during electrospinning. Polymer,40(16):4585-4592,1999.
35.Doshi J, Reneker DH. Electrospinning process and applications of electrospun fibers. Journal of Electrostatics,35(2-3):151-160,1995.
36.Zong XH, Kim K, Fang DF, Ran SF, Hsiao BS, Chu B. Structure and process relationship of electrospun bioabsorbable nanofiber membranes. Polymer, 43(16):4403-4412,2002.
37.Koski A, Yim K, Shivkumar S. Effect of molecular weight on fibrous PVA produced by electrospinning. Materials Letters,58(3-4):493-497,2004.
38.Megelski S, Stephens JS, Chase DB, Rabolt JF. Micro- and nanostructured surface morphology on electrospun polymer fibers. Macromolecules, 35(22):8456-8466 2002.
39.Li D, Xia YN. Fabrication of titania nanofibers by electrospinning. Nano Letters,3(4):555-560,2003.
40.Wannatong L, Sirivat A, Supaphol P. Effects of solvents on electrospun polymeric fibers:preliminary study on polystyrene. Polymer International , 53(11):1851-1859,2004.
41.Lee KH, Kim HY, La YM, Lee DR, Sung NH. Influence of a mixing solvent with tetrahydrofuran and N,N-dimethylformamide on electrospun poly(vinyl chloride) nonwoven mats. Journal of Polymer Science Part B-Polymer Physics , 40(19):2259-2268,2002.
42.G.T. Kim JSL, J.H. Shin, Y.C. Ahn, K.H. Jeong, C.M. Sung and J.K. Lee. Effect of humidity on the microstructures of electrospun polystyrene nanofibers. Microsc Microanal,10(2):554-555,2004.
43.Casper CL, Stephens JS, Tassi NG, Chase DB, Rabolt JF. Controlling surface morphology of electrospun polystyrene fibers:effect of humidity and molecular weight in the electrospinning process. Macromolecules,37(2):573-578,2004.
44.Duan B, Dong CH, Yuan XY, Yao KD. Electrospinning of chitosan solutions in acetic acid with poly(ethylene oxide). Journal of Biomaterials Science-Polymer Edition,15(6):797-811,2004.
45.Bhattarai N, Edmondson D, Veiseh O, Matsen FA, Zhang M. Electrospun chitosan-based nanofibers and their cellular compatibility. Biomaterials, 26(31):6176-6184,2005.
46.Klossner RR, Queen HA, Coughlin AJ, Krause WE. Correlation of Chitosan's rheological properties and its ability to electrospin. Biomacromolecules,9(10):2947-2953,2008.
47.Zhang YZ, Su B, Ramakrishna S, Lim CT. Chitosan nanofibers from an easily electrospinnable UHMWPEO-doped chitosan solution system. Biomacromolecules,9(1):136-141,2008.
48.Kriegel C, Kit K, McClements D, Weiss J. Electrospinning of chitosan–poly(ethylene oxide) blend nanofibers in the presence of micellar surfactant solutions. Polymer,50(1):189-200,2009.
49.Zhang JF, Yang DZ, Xu F, Zhang ZP, Yin RX, Nie J. Electrospun core-shell structure nanofibers from homogeneous solution of poly(ethylene oxide)/chitosan. Macromolecules,42(14):5278-5284,2009.
50.Ma M. Size dependence of specific power absorption of Fe3O4 particles in AC magnetic field. Journal of Magnetism and Magnetic Materials,268(1-2):33-39 2004.
51.Aono H, Hirazawa H, Naohara T, Maehara T, Kikkawa H, Watanabe Y. Synthesis of fine magnetite powder using reverse coprecipitation method and its heating properties by applying AC magnetic field. Materials Research Bulletin,40(7):1126-1135,2005.
52.Kim DH, Kim KN, Kim KM, Shim IB, Lee MH, Lee YK. Tuning of magnetite nanoparticles to hyperthermic thermoseed by controlled spray method. Journal of Materials Science,41(22):7279-7282,2006.
53.Qu J, Liu G, Wang Y, Hong R. Preparation of Fe3O4–chitosan nanoparticles used for hyperthermia. Advanced Powder Technology,21(4):461-467,2010.
54.Kim DH, Kim KN, Kim KM, Lee YK. Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia. Journal of Biomedical Materials Research Part A,88A(1):1-11, 2009.
55.Sashiwa H, Yamamori N, Ichinose Y, Sunamoto J, Aiba S. Chemical modification of chitosan, 17 - Michael reaction of chitosan with acrylic acid in water. Macromolecular Bioscience,3(5):231-233,2003.
56.Mincheva R. Synthesis of polymer-stabilized magnetic nanoparticles and fabrication of nanocomposite fibers thereof using electrospinning. European Polymer Journal,44(3):615-627,2008.
57.林佳妏，氰基丙烯酸酯與幾丁聚醣衍生物之凝血性質及應用，國立成功大學化學工程研究所博士論文，2003.
58.Hirai A, Odani H, Nakajima A. Determination of degree of deacetylation of chitosan by H-1-NMR spectroscopy. Polymer Bulletin,26(1):87-94,1991.
59.Han J, Zhang J, Yin R, Ma G, Yang D, Nie J. Electrospinning of methoxy poly(ethylene glycol)-grafted chitosan and poly(ethylene oxide) blend aqueous solution. Carbohydrate Polymers,83(1):270-276,2011.
60.Li G, Jiang Y, Huang K, Ding P, Chen J. Preparation and properties of magnetic Fe3O4–chitosan nanoparticles. Journal of Alloys and Compounds,466(1-2):451-456,2008.
61.Hua MY, Yang HW, Chuang CK, Tsai RY, Chen WJ, Chuang KL, Chang YH, Chuang HC, Pang ST. Magnetic-nanoparticle-modified paclitaxel for targeted therapy for prostate cancer. Biomaterials,31(28):7355-7363,2010.
62.Wan SR, Huang JS, Yan HS, Liu KL. Size-controlled preparation of magnetite nanoparticles in the presence of graft copolymers. Journal of Materials Chemistry,16(3):298-303,2006.
63.Liu X. Synthesis of amino-silane modified superparamagnetic silica supports and their use for protein immobilization. Colloids and Surfaces A: Physicochemical and Engineering Aspects,238(1-3):127-131,2004.
64.Wang HG, Li YX, Sun L, Li YC, Wang W, Wang SA, Xu SF, Yang QB. Electrospun novel bifunctional magnetic-photoluminescent nanofibers based on Fe2O3 nanoparticles and europium complex. Journal of Colloid and Interface Science,350(2):396-401,2010.
65.Tan ST, Wendorff JH, Pietzonka C, Jia ZH, Wang GQ. Biocompatible and biodegradable polymer nanofibers displaying superparamagnetic properties. Chemphyschem,6(8):1461-1465 ,2005.
66.Zivanovic S, Li JJ, Davidson PM, Kit K. Physical, mechanical, and antibacterial properties of chitosan/PEO blend films. Biomacromolecules , 8(5):1505-1510,2007.
67.Wang M. Field-responsive superparamagnetic composite nanofibers by electrospinning. Polymer,45(16):5505-5514, 2004.
68.Ito A, Shinkai M, Honda H, Kobayashi T. Medical application of functionalized magnetic nanoparticles. Journal of Bioscience and Bioengineering,100(1):1-11,2005.