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  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/123456789/67657
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dc.contributor.advisor謝銘鈞(Ming-Jium Shieh)
dc.contributor.authorSheng-Chao Youen
dc.contributor.author游盛兆zh_TW
dc.date.accessioned2021-06-17T01:42:33Z-
dc.date.available2017-08-31
dc.date.copyright2017-08-31
dc.date.issued2017
dc.date.submitted2017-07-27
dc.identifier.citationReference
1. Kean, T. and M. Thanou, Biodegradation, biodistribution and toxicity of chitosan. Advanced Drug Delivery Reviews, 2010. 62(1): p. 3-11.
2. Pereira, P., et al., Biocompatibility of a self-assembled glycol chitosan nanogel. Toxicology in Vitro, 2015. 29(3): p. 638-646.
3. Yin, W., et al., Biocompatible and target specific hydrophobically modified glycol chitosan nanoparticles. Biointerphases, 2016. 11(4): p. 04B301.
4. Kim, K., et al., Physicochemical Characterizations of Self-Assembled Nanoparticles of Glycol Chitosan−Deoxycholic Acid Conjugates. Biomacromolecules, 2005. 6(2): p. 1154-1158.
5. Min, K.H., et al., Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin enhance the drug stability and tumor targeting in cancer therapy. Journal of Controlled Release, 2008. 127(3): p. 208-218.
6. Kim, J.-H., et al., Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel. Journal of Controlled Release, 2006. 111(1–2): p. 228-234.
7. Oh, I.-h., et al., Cancer cell-specific photoactivity of pheophorbide a–glycol chitosan nanoparticles for photodynamic therapy in tumor-bearing mice. Biomaterials, 2013. 34(27): p. 6454-6463.
8. Lee, S.J., et al., Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system. Biomaterials, 2011. 32(16): p. 4021-4029.
9. Chen, Y.-I., et al., Traceable Self-Assembly of Laser-Triggered Cyanine-Based Micelle for Synergistic Therapeutic Effect. Advanced Healthcare Materials, 2015. 4(6): p. 892-902.
10. Zhang, E., et al., Mechanistic study of IR-780 dye as a potential tumor targeting and drug delivery agent. Biomaterials, 2014. 35(2): p. 771-778.
11. Luo, S., et al., A review of NIR dyes in cancer targeting and imaging. Biomaterials, 2011. 32(29): p. 7127-7138.
12. Jaque, D., et al., Nanoparticles for photothermal therapies. Nanoscale, 2014. 6(16): p. 9494-9530.
13. Yue, C., et al., IR-780 dye loaded tumor targeting theranostic nanoparticles for NIR imaging and photothermal therapy. Biomaterials, 2013. 34(28): p. 6853-6861.
14. Wang, W., et al., Controls on Polymer Molecular Weight May Be Used To Control the Size of Palmitoyl Glycol Chitosan Polymeric Vesicles. Langmuir, 2001. 17(3): p. 631-636.
15. Yuan, A., et al., Self-assembled PEG-IR-780-C13 micelle as a targeting, safe and highly-effective photothermal agent for in vivo imaging and cancer therapy. Biomaterials, 2015. 51: p. 184-193.
16. Jiang, C., et al., Hydrophobic IR780 encapsulated in biodegradable human serum albumin nanoparticles for photothermal and photodynamic therapy. Acta Biomaterialia, 2015. 14: p. 61-69.
17. Qiao, H., et al., Kidney-specific drug delivery system for renal fibrosis based on coordination-driven assembly of catechol-derived chitosan. Biomaterials, 2014. 35(25): p. 7157-7171.
18. Yuan, Z.-x., et al., Specific Renal Uptake of Randomly 50% N-Acetylated Low Molecular Weight Chitosan. Molecular Pharmaceutics, 2009. 6(1): p. 305-314.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67657-
dc.description.abstract在過去的研究中指出生物相容性材料乙二醇幾丁聚醣能用來作為藥物載體。本篇研究利用光熱試劑IR-780修飾上乙二醇幾丁聚醣(glycol chitosan, GC)來形成一個兼具近紅外光影像和光熱化學治療功能的多功能藥物載體。GC-IR能有效的包覆化療藥物SN38形成粒徑200nm左右的奈米粒子SN38@GC-IR/NP。該粒子在給予近紅外光雷射後能升溫產生光熱效應,並且在體溫37℃環境下穩定的釋放藥物。在細胞實驗中,本篇研究使用大腸癌細胞HCT116來作為癌症治療模型。結果顯示SN38@GC-IR/NP的細胞毒性隨著濃度增加而上升,並在結合光熱效應後達到更佳的治療效果。在動物實驗中,SN38@GC-IR/NP經靜脈注射後在血液中的濃度快速下降,並且累積在肝臟和腎臟。推測原因是SN38@GC-IR/NP會被網狀內皮系統(reticuloendothelial system, RES) 辨識並捕捉,以及幾丁聚醣本身有腎臟標靶的性質。總結來說,SN38@GC-IR/NP是一個具有光熱化學治療效果的藥物載體。但是在臨床應用方面,標靶性質和血液中的滯留時間需要進一步的實驗探討。zh_TW
dc.description.abstractThe biocompatible material, glycol chitosan, was suggested to be used as a drug carrier in previous research. In this study, glycol chitosan was modified with a theranostic agent, IR-780, to achieve a multifunctional drug nano-carrier (GC-IR) for near-infrared (NIR) imaging and chemothermal therapy. GC-IR can encapsulate chemotherapeutic drug SN38 at a high drug loading efficiency and form nanoparticle (SN38@GC-IR/NP) with a diameter around 200nm. SN38@GC-IR/NP presented photothermal effect after NIR laser irradiation and showed sustaining drug release profile under 37℃. Using the colon cancer cell HCT116 as model, in in vitro experiment, SN38@GC-IR/NP showed dose-dependent cytotoxicity and enhanced therapeutic effect in combination with photothermal effect. In in vivo experiment, the concentration of SN38@GC-IR/NP decreased quickly in plasma after intravenous injection and accumulated in kidney and liver. The results were considered to be generated from the capture of reticuloendothelial system (RES) and renal-targeting characteristics of chitosan. In sum, SN38@GC-IR/NP was proved to be a drug nano-carrier with chemothermal therapeutic effect. However, further exploration on targeting property and retention time of the nanoparticle is necessary for clinical uses.en
dc.description.provenanceMade available in DSpace on 2021-06-17T01:42:33Z (GMT). No. of bitstreams: 1
ntu-106-R03548052-1.pdf: 1695188 bytes, checksum: 2597f5b9b6b209cacf3106951a46b184 (MD5)
Previous issue date: 2017
en
dc.description.tableofcontentsCONTENTS
致謝 i
中文摘要 ii
Abstract iii
CONTENTS iv
LIST OF SCHEMES vii
LIST OF TABLES viii
LIST OF FIGURES ix
Chapter 1 Introduction 1
Chapter 2 Material and Methods 3
2.1 Material 3
2.2 Preparations of different molecular weight GC 3
2.3 Synthesis of GC-IR 4
2.4 Characterization of GC-IR 5
2.5 Preparation of Empty@GC-IR/NP and SN38@GC-IR/NP 5
2.6 Characterization of Empty@GC-IR/NP and SN38@GC-IR/NP 6
2.7 Photothermal properties of SN38@GC8-IR-4/NP 6
2.8 Drug release profile 7
2.9 Cellular uptake 7
2.10 in vitro Cytotoxicity 8
2.11 Animal and tumor model 8
2.12 in vivo imaging 9
2.13 Pharmacokinetic analysis 9
Chapter 3 Result & Discussion 10
3.1 Preparations of different molecular weight GC 10
3.2 Synthesis and characterization of GC-IR 10
3.3 Characterization of Empty@GC-IR/NP and SN38@GC-IR/NP 12
3.4 Photothermal effect of SN38@GC8-IR-4/NP 14
3.5 in vitro Drug Release profile 15
3.6 In vitro Cellular uptake 15
3.7 In vitro Cytotoxicity 16
3.8 In vivo Imaging of SN38@GC8-IR-4/NP 16
3.9 Pharmacokinetic Analysis of SN38@GC8-IR-4/NP 17
Chapter 4 Conclusions 19
Reference 20
Scheme 23
Table 24
Figure 26
dc.language.isoen
dc.subject奈米顆粒zh_TW
dc.subject乙二醇幾丁聚醣zh_TW
dc.subject光熱試劑zh_TW
dc.subject近紅外光影像zh_TW
dc.subject光熱治療zh_TW
dc.subjectglycol chitosanen
dc.subjecttheranostic agenten
dc.subjectnanoparticleen
dc.subjectnear-infrared (NIR) imagingen
dc.subjectphotothermal therapy (PTT)en
dc.title以接枝光熱試劑之乙二醇幾丁聚醣為藥物載體在腫瘤治療上之評估zh_TW
dc.titleEvaluation of Theranostic Agent Modified Glycol Chitosan as a Drug Carrier on Cancer Therapyen
dc.typeThesis
dc.date.schoolyear105-2
dc.description.degree碩士
dc.contributor.oralexamcommittee林文澧(Win-Li Lin),張富雄(Fu-Hsiung Chang),駱俊良(Chun-Liang Lo),胡尚秀(Shang-Hsiu Hu)
dc.subject.keyword乙二醇幾丁聚醣,光熱試劑,奈米顆粒,近紅外光影像,光熱治療,zh_TW
dc.subject.keywordglycol chitosan,theranostic agent,nanoparticle,near-infrared (NIR) imaging,photothermal therapy (PTT),en
dc.relation.page32
dc.identifier.doi10.6342/NTU201700710
dc.rights.note有償授權
dc.date.accepted2017-07-28
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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