Skip navigation

DSpace

機構典藏 DSpace 系統致力於保存各式數位資料(如:文字、圖片、PDF)並使其易於取用。

點此認識 DSpace
DSpace logo
English
中文
  • 瀏覽論文
    • 校院系所
    • 出版年
    • 作者
    • 標題
    • 關鍵字
    • 指導教授
  • 搜尋 TDR
  • 授權 Q&A
    • 我的頁面
    • 接受 E-mail 通知
    • 編輯個人資料
  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 醫學工程學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44302
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor謝銘鈞
dc.contributor.authorLi-Yuan Yangen
dc.contributor.author楊鯉源zh_TW
dc.date.accessioned2021-06-15T02:49:54Z-
dc.date.available2011-08-18
dc.date.copyright2009-08-18
dc.date.issued2009
dc.date.submitted2009-08-05
dc.identifier.citation1. Dougherty, T.J., et al., Photodynamic therapy. J Natl Cancer Inst, 1998. 90(12): p. 889-905.
2. Juarranz, A., et al., Photodynamic therapy of cancer. Basic principles and applications. Clin Transl Oncol, 2008. 10(3): p. 148-54.
3. Schmidt-Erfurth, U. and T. Hasan, Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration. Surv Ophthalmol, 2000. 45(3): p. 195-214.
4. Weishaupt, K.R., C.J. Gomer, and T.J. Dougherty, IDENTIFICATION OF SINGLET OXYGEN AS CYTOTOXIC AGENT IN PHOTO-INACTIVATION OF A MURINE TUMOR. Cancer Research, 1976. 36(7): p. 2326-2329.
5. Henderson, B.W. and T.J. Dougherty, HOW DOES PHOTODYNAMIC THERAPY WORK. Photochemistry and Photobiology, 1992. 55(1): p. 145-157.
6. Castano, A.P., Q. Liu, and M.R. Hamblin, A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy. British Journal of Cancer, 2006. 94(3): p. 391-397.
7. Wagnieres, G., et al., Clinical evaluation of the cutaneous phototoxicity of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin. Photochem Photobiol, 1998. 68(3): p. 382-7.
8. McCaughan, J.S., Jr., Photodynamic therapy: a review. Drugs Aging, 1999. 15(1): p. 49-68.
9. Pegaz, B., et al., Photothrombic activity of m-THPC-loaded liposomal formulations: pre-clinical assessment on chick chorioallantoic membrane model. Eur J Pharm Sci, 2006. 28(1-2): p. 134-40.
10. Dragicevic-Curic, N., et al., Temoporfin-loaded invasomes: development, characterization and in vitro skin penetration studies. J Control Release, 2008. 127(1): p. 59-69.
11. Gravier, J., et al., Improvement of meta-tetra(hydroxyphenyl)chlorin-like photosensitizer selectivity with folate-based targeted delivery. synthesis and in vivo delivery studies. J Med Chem, 2008. 51(13): p. 3867-77.
12. Lee, S.J., et al., Tumor specificity and therapeutic efficacy of photosensitizer-encapsulated glycol chitosan-based nanoparticles in tumor-bearing mice. Biomaterials, 2009. 30(15): p. 2929-39.
13. Khdair, A., et al., Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro. Eur J Pharm Biopharm, 2009. 71(2): p. 214-22.
14. Hofman, J.W., et al., Photocytotoxicity of mTHPC (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation. Pharm Res, 2008. 25(9): p. 2065-73.
15. Bae, Y., et al., Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjug Chem, 2005. 16(1): p. 122-30.
16. Nishiyama, N., et al., Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice. Cancer Research, 2003. 63(24): p. 8977-8983.
17. Gref, R., et al., 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. Colloids and Surfaces B-Biointerfaces, 2000. 18(3-4): p. 301-313.
18. Zambaux, M.F., et al., MPEO-PLA nanoparticles: Effect of MPEO content on some of their surface properties. Journal of Biomedical Materials Research, 1999. 44(1): p. 109-115.
19. Engin, K., et al., Extracellular pH distribution in human tumours. Int J Hyperthermia, 1995. 11(2): p. 211-6.
20. Lee, E.S., K. Na, and Y.H. Bae, Super pH-sensitive multifunctional polymeric micelle. Nano Lett, 2005. 5(2): p. 325-9.
21. Lee, E.S., et al., Super pH-sensitive multifunctional polymeric micelle for tumor pH(e) specific TAT exposure and multidrug resistance. J Control Release, 2008. 129(3): p. 228-36.
22. Lee, E.S., Z. Gao, and Y.H. Bae, Recent progress in tumor pH targeting nanotechnology. J Control Release, 2008. 132(3): p. 164-70.
23. Lee, E.S., K. Na, and Y.H. Bae, Polymeric micelle for tumor pH and folate-mediated targeting. J Control Release, 2003. 91(1-2): p. 103-13.
24. Kathmann, E.E.L., L.A. White, and C.L. McCormick, Water-soluble polymers .73. Electrolyte- and pH-responsive zwitterionic copolymers of 4-[(2-acrylamido-2-methylpropyl)dimethylammonio]butanoate with 3-[(2-acrylamido-2-methylpropyl)dimethylammonio]propanesulfonate. Macromolecules, 1997. 30(18): p. 5297-5304.
25. Liu, Y. and R. Guo, pH-dependent structures and properties of casein micelles. Biophys Chem, 2008. 136(2-3): p. 67-73.
26. Hu, Y.Q., et al., RAFT synthesis of amphiphilic (A-ran-B)-b-C diblock copolymers with tunable pH-sensitivity. Journal of Polymer Science Part a-Polymer Chemistry, 2008. 46(11): p. 3740-3748.
27. Dayananda, K., et al., Synthesis and characterization of MPEG-b-PDPA amphiphilic block copolymer via atom transfer radical polymerization and its pH-Dependent micellar behavior. Macromolecular Research, 2007. 15(4): p. 385-391.
28. Styrkas, D.A., et al., pH-controlled adsorption of polyelectrolyte diblock copolymers at the solid/liquid interface. Langmuir, 2000. 16(14): p. 5980-5986.
29. Licciardi, M., et al., Synthesis of novel folic acid-functionalized biocompatible block copolymers by atom transfer radical polymerization for gene delivery and encapsulation of hydrophobic drugs. Biomacromolecules, 2005. 6(2): p. 1085-96.
30. Shalaan, E. and H. Schmitt. Mg nanoparticle switchable mirror films with improved absorption-desorption kinetics. 2006: Surface science 600:1818, 3650-3653
31. Kalyanasundaram, K. and J.K. Thomas, ENVIRONMENTAL EFFECTS ON VIBRONIC BAND INTENSITIES IN PYRENE MONOMER FLUORESCENCE AND THEIR APPLICATION IN STUDIES OF MICELLAR SYSTEMS. Journal of the American Chemical Society, 1977. 99(7): p. 2039-2044.
32. Gerlier, D. and N. Thomasset, USE OF MTT COLORIMETRIC ASSAY TO MEASURE CELL ACTIVATION. Journal of Immunological Methods, 1986. 94(1-2): p. 57-63.
33. Hu, Y.Q., et al., Synthesis and pH-dependent micellization of 2-(diisopropylamino)ethyl methacrylate based amphiphilic diblock copolymers via RAFT polymerization. Polymer, 2007. 48(12): p. 3437-3443.
34. van Sluis, R., et al., In vivo imaging of extracellular pH using H-1 MRSI. Magnetic Resonance in Medicine, 1999. 41(4): p. 743-750.
35. Ojugo, A.S.E., et al., Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous F-19 and P-31 probes. Nmr in Biomedicine, 1999. 12(8): p. 495-504.
36. Maeda, H., et al., Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of Controlled Release, 2000. 65(1-2): p. 271-284.
37. Litzinger, D.C., et al., Effect of Liposome Size on the Circulation Time and Intraorgan Distribution of Amphipathic Poly(Ethylene Glycol)-Containing Liposomes. Biochimica Et Biophysica Acta-Biomembranes, 1994. 1190(1): p. 99-107.
38. Melnikova, V.O., et al., Subcellular localization of meta-tetra(hydroxyphenyl) chlorin in human tumor cells subjected to photodynamic treatment. Journal of Photochemistry and Photobiology B-Biology, 1999. 49(2-3): p. 96-103.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/44302-
dc.description.abstract光動力療法(PDT)是一個有效治療腫瘤的方法,其方法是給予光感藥物後再照光以達到療效。然而,光感藥物有著不溶於水且對腫瘤沒有選擇性的缺點。為了以在腫瘤中的酸性環境為目標,我們使用AIBN為initiator合成了PEGMA-co-DPA這個分子聚合物,並以此聚合物做成了對酸鹼值敏感的奈米粒子來包覆光感藥物-間–四羥基氯苯酚 (m-THPC)。我們使用核磁共振儀及凝膠滲透層析來分析我們合成的分子聚合物,並使用pyrene作為探針來研究酸鹼度對於次分子聚合物形成奈米粒子和其臨界聚合濃度(CAC)的影響。結果顯示在此合成的分子聚合物的臨界聚合酸鹼值在5.8到6.6之間,臨界聚合濃度則是在0.0045%到0.0089%之間。之後我們以oil-in-water的方式製備了包覆m-THPC的奈米粒子,並使用動態光散射儀(DLS)以及穿透式電子顯微鏡(TEM)觀察奈米粒子,發現此奈米粒子為圓形且大小約為132奈米,包覆率為89%。在釋放速率的實驗方面,結果顯示了放置48小時後,此奈米粒子在酸鹼值為5的環境下釋放了58%的藥物,比在酸鹼值為7的環境下的10%還多。另外我們使用HT-29這株細胞來研究此奈米粒子的光動力療法效果。以上這些結果顯示了我們製備的對酸鹼度敏感的奈米粒子有針對腫瘤的潛力。zh_TW
dc.description.abstractPhotodynamic therapy (PDT) is an effective therapy for tumor, which involves the administration of photosensitizers followed by illumination. However, the insolubility and non-targeting are defects of photosensitizers. For targeting the acid environment at tumor site, Poly(ethylene glycol) methacrylate-co-2-(Diisopropylamino) ethyl methacrylate (PEGMA-co-DPA) copolymers were synthesized in the presence of 2,2’-Azobis-isobutyronitrile (AIBN) and then formed pH sensitive nanoparticles to encapsulate a photosensitizer, m-THPC. The characteristic of these copolymers were evaluated by 1H nuclear magnetic resonance and gel permeation chromatography. The pH effect on aggregation/deaggregation and critical aggregation concentration (CAC) of the nanoparticles was studied by using pyrene as a probe. The results showed that the critical aggregation pH (Ph*) of the polymers were from 5.8 to 6.6 and the CAC were from 0.0045 to 0.0089 wt% at pH 7.4. The m-THPC loaded nanoparticles were prepared by oil-in-water. The size and morphology of nanoparticles were observed using dynamic light scattering and transmission electron microscopy. The results indicated that the nanoparticles were sphere and the size was 132 nm. The drug encapsulation efficiency was 89%. The in vitro release profile performed that the release rate of m-THPC at pH 5.0 (58% m-THPC released within 48 hours) was faster than at pH 7.0 (10% m-THPC released within 48 hours). The in vitro PDT efficiency was tested with HT-29 cell line by MTT assay. These findings suggest that the pH sensitive nanoparticles prepared in this study are potential carriers for tumor targeting.en
dc.description.provenanceMade available in DSpace on 2021-06-15T02:49:54Z (GMT). No. of bitstreams: 1
ntu-98-R96548049-1.pdf: 2798651 bytes, checksum: bfd38694504f6334b9597d2bff404222 (MD5)
Previous issue date: 2009
en
dc.description.tableofcontents目 錄
口試委員會審定書……….……………………………………………….. i
誌謝………………………………………………………………………...ii
中文摘要…………………………………………………………….…....iii
英文摘要………………………………………………………….……. iv
1. Introduction………………………………………….………….……... 1
2. Materials and Methods………….……………………………….…...... 5
2.1 Materials………………………………………………………..….. 6
2.2. Synthesis of PEGMA-co-DPA……….….……….…………..…… 8
2.3. Copolymer characterizations……………………………….………8
2.4. Nanoparticle formation……………………….……………………8
2.5. Nanoparticle Characterization……………………………….……..9
2.6. Cell culture……………………...……………..………….………11
2.7. In vitro cytotoxicity in dark…..………………………….………..11
2.8. Cellular uptake…………………………………………..………..12
2.9. Confocal laser scanning microscopy……………………….……..13
2.10. Photodynamic therapy efficiency of m-THPC loaded nanoparticles…………………………………………….……....13
3. Results……………………….………………………………….……..14
3.1. Synthesis and characterize of PEGMA-co-DPA…………………14
3.2. Nanoparticle characterization…………………………………….14
3.3. In vitro cytotoxicity of nanoparticles…………………………….18
3.4. Cellular uptake………………………………………..….………18
3.5. Photodynamic therapy efficiency………………………..……….19
4. Discussion……...…………………………………….………………..20
5. Conclusion……………………………………………………….…….24
參考文獻……………………………………………….……….……….. 25
附錄………………………………………….…………………………... 31
dc.language.isoen
dc.subject間–四羥基氯苯酚zh_TW
dc.subject光動力療法zh_TW
dc.subject腫瘤zh_TW
dc.subject光感藥物zh_TW
dc.subject對酸鹼值敏感的奈米粒子zh_TW
dc.subjecttumoren
dc.subjectm-THPCen
dc.subjectpH sensitive nanoparticlesen
dc.subjectphotosensitizersen
dc.subjectPhotodynamic therapyen
dc.title合成並探討PEGMA-co-DPA奈米粒子之特性及其在光動力療法上之應用zh_TW
dc.titleSynthesis and Characterization of PEG-co-DPA Nanoparticles and Application of Photodynamic Therapyen
dc.typeThesis
dc.date.schoolyear97-2
dc.description.degree碩士
dc.contributor.oralexamcommittee楊禎明,賴秉杉,婁培人
dc.subject.keyword光動力療法,腫瘤,光感藥物,對酸鹼值敏感的奈米粒子,間–四羥基氯苯酚,zh_TW
dc.subject.keywordPhotodynamic therapy,tumor,photosensitizers,pH sensitive nanoparticles,m-THPC,en
dc.relation.page52
dc.rights.note有償授權
dc.date.accepted2009-08-05
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
顯示於系所單位:醫學工程學研究所

文件中的檔案:
檔案 大小格式 
ntu-98-1.pdf
  未授權公開取用
2.73 MBAdobe PDF
顯示文件簡單紀錄


系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。

社群連結
聯絡資訊
10617臺北市大安區羅斯福路四段1號
No.1 Sec.4, Roosevelt Rd., Taipei, Taiwan, R.O.C. 106
Tel: (02)33662353
Email: ntuetds@ntu.edu.tw
意見箱
相關連結
館藏目錄
國內圖書館整合查詢 MetaCat
臺大學術典藏 NTU Scholars
臺大圖書館數位典藏館
本站聲明
© NTU Library All Rights Reserved