請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64933完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔡偉博(Wei-Bor Tsai) | |
| dc.contributor.author | Hsin-Yu Lai | en |
| dc.contributor.author | 賴心譽 | zh_TW |
| dc.date.accessioned | 2021-06-16T23:08:46Z | - |
| dc.date.available | 2016-08-09 | |
| dc.date.copyright | 2012-08-09 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-04 | |
| dc.identifier.citation | 1. Fang, J., H. Nakamura, and H. Maeda, The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Advanced Drug Delivery Reviews. 63(3): p. 136-151.
2. Torchilin, V., Tumor delivery of macromolecular drugs based on the EPR effect. Advanced Drug Delivery Reviews. 63(3): p. 131-135. 3. Bisht, S. and A. Maitra, Dextran–doxorubicin/chitosan nanoparticles for solid tumor therapy. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2009. 1(4): p. 415-425. 4. Maeda, H., SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy. Advanced Drug Delivery Reviews, 2001. 46: p. 169-185. 5. Kope?ek, J.i., et al., HPMA copolymer-anticancer drug conjugates: design, activity, and mechanism of action. European Journal of Pharmaceutics and Biopharmaceutics, 2000. 50(1): p. 61-81. 6. Mitra, S., et al., Tumour targeted delivery of encapsulated dextran-doxorubicin conjugate using chitosan nanoparticles as carrier. Journal of Controlled Release, 2001. 74: p. 317-323. 7. Mayer, L.D., et al., Characterization of liposomal systems containing doxorubicin entrapped in response to pH gradients. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1990. 1025(2): p. 143-151. 8. Parisa Yousefpour, F.A., Ebrahim Vashegani Farahani3,Ramin Sakhtianchi,Rassoul Dinarvand, Polyanionic carbohydrate doxorubicin–dextran nanocomplex as a delivery system for anticancer drugs: in vitro analysis and evaluations. Nanomedicine 2011. 6: p. 9. 9. Hans, M.L. and A.M. Lowman, Biodegradable nanoparticles for drug delivery and targeting. Current Opinion in Solid State and Materials Science, 2002. 6(4): p. 319-327. 10. Bhattacharjee, J., et al., Small angle neutron scattering study of doxorubicin-surfactant complexes encapsulated in block copolymer micelles. Pramana, 2008. 71(5): p. 991-995. 11. Shuai, X., et al., Micellar carriers based on block copolymers of poly(e-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. Journal of Controlled Release, 2004. 98(3): p. 415-426. 12. Jeong, Y.-I.L., K.-D. Chung, and K. Choi, Doxorubicin release from self-assembled nanoparticles of deoxycholic acid-conjugated dextran. Archives of Pharmacal Research. 34(1): p. 159-167. 13. Licciardi, M., et al., Polyaspartamide-graft-Polymethacrylate Nanoparticles for Doxorubicin Delivery. Macromolecular Bioscience. 11(3): p. 445-454. 14. Lavasanifar, A., J. Samuel, and G.S. Kwon, Poly(ethylene oxide)-block-poly(l-amino acid) micelles for drug delivery. Advanced Drug Delivery Reviews, 2002. 54(2): p. 169-190. 15. Rodrigues, P.C.A., et al., Acid-sensitive polyethylene glycol conjugates of doxorubicin: preparation, in vitro efficacy and intracellular distribution. Bioorganic & Medicinal Chemistry, 1999. 7(11): p. 2517-2524. 16. Zhou, L., et al., Endosomal pH-Activatable Poly(ethylene oxide)-graft-Doxorubicin Prodrugs: Synthesis, Drug Release, and Biodistribution in Tumor-Bearing Mice. Biomacromolecules. 12(5): p. 1460-1467. 17. Young Lee, G., et al., Anti-tumor and anti-metastatic effects of gelatin-doxorubicin and PEGylated gelatin-doxorubicin nanoparticles in SCC7 bearing mice. Journal of Drug Targeting, 2006. 14(10): p. 707-716. 18. Duncan, R., et al., Polymer-drug conjugates, PDEPT and PELT: basic principles for design and transfer from the laboratory to clinic. Journal of Controlled Release, 2001. 74: p. 135-146. 19. Akagi, T., et al., Pharmaceutical and Medical Applications of Poly-Gamma-Glutamic Acid Amino-Acid Homopolymers Occurring in Nature, Springer Berlin / Heidelberg. p. 119-153. 20. Akao, T., et al., A poly(g-glutamic acid)-amphiphile complex as a novel nanovehicle for drug delivery system. Journal of Drug Targeting. 18(7): p. 550-556. 21. Liang, H.-F., et al., Paclitaxel-loaded poly(g-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials, 2006. 27(9): p. 2051-2059. 22. Manocha, B. and A. Margaritis, Controlled Release of Doxorubicin from Doxorubici;-Polyglutamic Acid Ionic Complex. Journal of Nanomaterials. 2010. 23. Al-Ghamdi, S.S., Time and Dose Dependent Study of Doxorubicin Induced du-145 Cytotoxicity. Drug Metabolism Letters, 2008. 2(1). 24. Betancourt, T., B. Brown, and L. Brannon-Peppas, Doxorubicin-loaded PLGA nanoparticles by nanoprecipitation: preparation, characterization and in?vitro evaluation. Nanomedicine, 2007. 2(2): p. 219-232. 25. Zhang, J., et al., Self-assembled nanoparticles based on hydrophobically modified chitosan as carriers for doxorubicin. Nanomedicine: Nanotechnology, Biology and Medicine, 2007. 3(4): p. 258-265. 26. Senter, P.D. and C.J. Springer, Selective activation of anticancer prodrugs by monoclonal antibody Enzyme conjugates. Advanced Drug Delivery Reviews, 2001. 53(3): p. 247-264. 27. Lee, G.Y., et al., Peptide-doxorubicin conjugates specifically degraded by matrix metalloproteinases expressed from tumor. Drug Development Research, 2006. 67(5): p. 438-447. 28. Dubowchik, G.M. and M.A. Walker, Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs. Pharmacology & Therapeutics, 1999. 83(2): p. 67-123. 29. Garnett, M.C., Targeted drug conjugates: principles and progress. Advanced Drug Delivery Reviews, 2001. 53(2): p. 171-216. 30. Bagalkot, V., et al., An Aptamer–Doxorubicin Physical Conjugate as a Novel Targeted Drug-Delivery Platform. Angewandte Chemie International Edition, 2006. 45(48): p. 8149-8152. 31. Madhankumar, A.B., et al., Efficacy of interleukin-13 receptor targeted liposomal doxorubicin in the intracranial brain tumor model. Molecular Cancer Therapeutics, 2009. 8(3): p. 648-654. 32. Al-Qubaisi, M., et al., Selective Cytotoxicity of Goniothalamin against Hepatoblastoma HepG2 Cells. Molecules. 16(4): p. 2944-2959. 33. Liang, H.-F., et al., Preparation of nanoparticles composed of poly(r-glutamic acid)-poly(lactide) block copolymers and evaluation of their uptake by HepG2 cells. Journal of Controlled Release, 2005. 105(3): p. 213-225. 34. Pimm, M.V., et al., Gamma Scintigraphy of a 123I-Labelled N-(2-Hydroxypropyl)Methacrylamide Copolymer-Doxorubicin Conjugate Containing Galactosamine Following Intravenous Administration to Nude Mice Bearing Hepatic Human Colon Carcinoma. Journal of Drug Targeting, 1996. 3(5): p. 385-390. 35. Takahashi, T., et al., A fluorimetric Morgan-Elson assay method for hyaluronidase activity. Analytical Biochemistry, 2003. 322(2): p. 257-263. 36. Roseman, S. and I. Daffner, Colorimetric Method for Determination of Glucosamine and Galactosamine. Analytical Chemistry, 1956. 28(11): p. 1743-1746. 37. Zaman, N.T., Targeted Stimuli-Responsive Dextran Conjugates for Doxorubicin Delivery to Hepatocytes Institute of Bioengineering and Nanotechnology, 38 Biopolis Way, The Nanos, Singapore 138669 2005. 39. Muckenschnabel, I., et al., Quantitation of hyaluronidases by the Morgan-Elson reaction: comparison of the enzyme activities in the plasma of tumor patients and healthy volunteers. Cancer Letters, 1998. 131(1): p. 13-20. 40. Beau, J.-M., P. Rollin, and P. Sina, Structure du chromogne i de la action de morgan-Eljon. Carbohydrate Research, 1977. 53(2): p. 187-195. 41. Shakeri-Zadeh, A., Cancerous Cells Targeting and Destruction Using Folate Conjugated Gold Nanoparticles. Dynamic Biochemistry,Process Biotechnology and Molecular Biology, 2010. 4: p. 6. 42. Wang, Y., et al., Targeted delivery of doxorubicin into cancer cells using a folic acid-dendrimer conjugate. Polymer Chemistry. 2(8): p. 1754-1760. 43. Husseini, G.A. and W.G. Pitt, Micelles and nanoparticles for ultrasonic drug and gene delivery. Advanced Drug Delivery Reviews, 2008. 60(10): p. 1137-1152. 44. Arthur, C., et al., The effect of ultrasonic irradiation on doxorubicin-induced cytotoxicity in three human bladder cancer cell lines. Ultrasonics, 2007. 46(1): p. 68-73. 45. Yoshida, T., et al., Combination of doxorubicin and low-intensity ultrasound causes a synergistic enhancement in cell killing and an additive enhancement in apoptosis induction in human lymphoma U937 cells. Cancer Chemotherapy and Pharmacology, 2008. 61(4): p. 559-567. 46. Marin, A., et al., Drug delivery in pluronic micelles: effect of high-frequency ultrasound on drug release from micelles and intracellular uptake. Journal of Controlled Release, 2002. 84: p. 39-47. 47. Wagner, W.D., A more sensitive assay discriminating galactosamine and glucosamine in mixtures. Analytical Biochemistry, 1979. 94(2): p. 394-396. 48. Keresztessy, Z., et al., Self-assembling chitosan/poly-γ-glutamic acid nanoparticles for targeted drug delivery. Colloid & Polymer Science, 2009. 287(7): p. 759-765. 49. Yoshikawa, T., et al., Development of amphiphilic r-PGA-nanoparticle based tumor vaccine: Potential of the nanoparticulate cytosolic protein delivery carrier. Biochemical and Biophysical Research Communications, 2008. 366(2): p. 408-413. 50. Liang, H.-F., et al., Paclitaxel-Loaded Poly(r-glutamic acid)-poly(lactide) Nanoparticles as a Targeted Drug Delivery System against Cultured HepG2 Cells. Bioconjugate Chemistry, 2006. 17(2): p. 291-299. 51. Yoo, H.S., et al., In vitro and in vivo anti-tumor activities of nanoparticles based on doxorubicin-PLGA conjugates. Journal of Controlled Release, 2000. 68(3): p. 419-431. 52. Hashida, M., et al., Design of polymeric prodrugs of prostaglandin E1 having galactose residue for hepatocyte targeting. Journal of Controlled Release, 1999. 62: p. 253-262. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64933 | - |
| dc.description.abstract | 在以靜脈注射抗癌藥物的癌症治療中,最常見的問題就是抗癌藥物小分子注射進入血液以後會快速的擴散到全身,除了進入癌組織以外,同時也進入正常組織中進而傷害正常細胞。在這個研究中,以高分子做為藥物的載體,並接枝可被特定細胞辨識的分子(ligand)來達到標的的效果,最後加上超音波提高治療效果。在研究的一開始,我們以親水性的高分子聚麩胺酸(γ-PGA)做為疏水性抗癌藥物艾黴素(Doxorubicin)的載體並利用簡單的化學合成方法EDC/NHS的方式將藥物接枝到高分子上,並利用粒徑分析儀測得高分子-藥物的大小 < 200 nm,推測高分子-藥物在水溶液中可能藉由親疏水性發生聚集現象,並且在細胞實驗中觀察到此種聚集奈米顆粒可以降低艾黴素的毒性。另外,當探討同時接枝可以被細胞辨識的分子如半乳糖胺(Galactosamine)或葉酸(Folic acid)至聚麩胺酸-艾黴素時,可看出半乳糖胺是有比較好的治療效果,同時也嘗試了不同的艾黴素與半乳糖的接枝比例,可以看出在高分子單體:艾黴素:半乳糖等於10:2:8的理論接枝條件下,相較於未接枝半乳糖的聚麩胺酸-艾黴素是有比較好的細胞毒殺效果。接下來在以此條件來進行超音波的實驗,並比較加超音波的前後對於細胞毒殺效果的影響。在實驗中可以發現加了超音波以後,在加入低濃度藥物的組別裡,明顯提高毒殺效果。另外我們也用螢光顯微鏡觀察細胞吸收藥物的情況,經由DAPI染細胞核比對,可以發現藥物確實是進入細胞核中,並由定量的結果得到在3小時的培養後,細胞吸收的藥量以聚麩胺酸-艾黴素-半乳糖胺是比艾黴素及聚麩胺酸-艾黴素明顯較多,加入超音波以後,細胞吸收藥量的結果差異較為不明顯。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-16T23:08:46Z (GMT). No. of bitstreams: 1 ntu-101-R99524081-1.pdf: 3422010 bytes, checksum: aac353364491726511746eae55f9ace8 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Acknowledgment.... i
Abstract..........ii Content...........v List of Tables...vii List of Figures..viii Chapter 1 Introduction.....................................1 1.1 Common strategies of drug carrier design for EPR effect ....................................................1 1.1.1 EPR effect..........................................1 1.1.2 Classification of drug carrier design...............4 1.2 Polymer conjugate with drugs to form nanopaticles for cancerous therapy.........................................11 1.2.1 Gamma-poly-glutamic acid,γ-PGA.....................11 1.2.2 Doxorubicin, DXR...................................16 1.3 Target drugs to cancer cells.........................20 1.3.1 Methods of targeting drug to cancer cells..........20 1.3.2 Galactosamine(Gal) for targeting to liver cancer cells.....................................................22 1.3.3 Folic acid(FA)for targeting to cancer cells........25 1.4 Ultrasound for helping cells uptake..................27 1.5 Motive and Aims......................................29 1.6 Research framework...................................30 Chapter 2 Materials and Methods...........................32 2.1 Materials............................................32 2.1.1 Synthesis of γ-PGA-Doxorubicin and γ-PGA-Doxorubicin-Galactosamine andγ-PGA-Doxorubicin-Folic acid.............32 2.1.2 BNL cell culture...................................32 2.1.3 Morgan-Elson assay.................................33 2.1.4 Cell viability.....................................33 2.1.5 Cell uptake .......................................34 2.2 Experimental equipments..............................34 2.3 Solution formula.....................................35 2.4 Methods..............................................37 2.4.1 Preparation of γ-PGA conjugated with doxorubicin and galactosamine and folic acid to form nanoparticles........37 2.4.2 Elson-Morgan assay for galactosamine...............39 2.4.3 Size and zeta potential............................40 2.4.4 Ultrasound treatment ..............................40 2.4.5 Cellviability......................................42 2.4.6 Cell uptake .......................................42 2.4.7 Statistic analysis.................................43 Chapter 3 Results and Discussion.........................44 3.1 The characterization of γ-PGA-Doxorubicin and γ-PGA-Doxorubicin-Galactosamine.................................44 3.2 Size and zeta potential..............................47 3.3 Cell viability.......................................49 3.4 Cell uptake..........................................54 3.5 Discussion...........................................56 Chapter 4 Conclusion......................................84 Chapter 5 Future work.....................................86 Reference.................................................87 | |
| dc.language.iso | zh-TW | |
| dc.subject | 半乳糖胺 | zh_TW |
| dc.subject | 超音波 | zh_TW |
| dc.subject | 艾黴素 | zh_TW |
| dc.subject | 聚麩胺酸 | zh_TW |
| dc.subject | γ-PGA | en |
| dc.subject | doxorubicin | en |
| dc.subject | galactosamine | en |
| dc.subject | ultrasound | en |
| dc.title | 利用聚麩胺酸做為艾黴素之載體於肝癌細胞之治療 | zh_TW |
| dc.title | Using γ-PGA as Carrier of Doxorubicin for Liver
Cancer Cells Therapy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 游佳欣,陳文翔,劉澤英 | |
| dc.subject.keyword | 聚麩胺酸,艾黴素,半乳糖胺,超音波, | zh_TW |
| dc.subject.keyword | γ-PGA,doxorubicin,galactosamine,ultrasound, | en |
| dc.relation.page | 91 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-06 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 化學工程學研究所 | zh_TW |
| 顯示於系所單位: | 化學工程學系 | |
文件中的檔案:
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-101-1.pdf 未授權公開取用 | 3.34 MB | Adobe PDF |
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。
