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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 謝銘鈞 | |
dc.contributor.author | Wen-Yu Chu | en |
dc.contributor.author | 竺玟妤 | zh_TW |
dc.date.accessioned | 2021-06-08T00:06:29Z | - |
dc.date.copyright | 2013-08-20 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-12 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17316 | - |
dc.description.abstract | 光動力療法是一種低侵入性的新興治療癌症的方式,相較於傳統的外科手術或放射線治療具有以下優勢:光感物質可重複注射,以及對病變組織可重複給與光照,再加上光動力治療只影響光照區域,因此治療範圍侷限在腫瘤組織上而較不影響正常組織。光動力治療為一光化學反應,其原理是當光感藥物吸收特定波長的光能量由基態躍升至激發態,若電子直接回到基態並釋放可偵測螢光,此特性可以應用於光動力診斷 ; 但若被激發的光感藥物在單相態發生電子旋轉或能量轉移進而產生單態氧(Singlet oxygen, 1O2)物質或是活性氧物質(Reactive oxygen species, ROS)來達到治療的效果。然而,應用最大限制在於大多光感藥物不溶於水且對腫瘤親和性不足。
本論文的研究著重於發展多功能性的奈米微胞進行光動力診斷及治療的應用。載體部分,合成具有酸檢應答性共聚物PEGMA-co-DPA以及生物可降解性雙聚團共聚物mPEG-b-PCL 組成複合性奈米微胞,作為包覆疏水性光感藥物 Chlorin e6 奈米載體;此外,為了提升腫瘤的標靶能力,於複合性奈米微胞表面進行EGFR 胜肽(GE11)的接枝。研究首先合成一系列不同比例的酸檢應答性共聚物,由電位滴定法測定當PEGMA/DPA重量比為1:2時,其PKa值為6.89,此pH值位於腫瘤酸性微環境範圍內(pH=5.7~7.0) ,可以做為腫瘤酸性微環境藥物釋放之應用。接著探討不同重量比例組成下接枝共聚物/雙團聯共聚物對於複合型微胞粒徑之影響,結果顯示接枝共聚物/雙團聯共聚物重量比例為5:5時有最佳的粒徑約91.05nm並且有較小的CMC值,之後以oil-in-water的方式製備了包覆Chlorin e6的複合性奈米微胞,接枝GE11的複合性奈米微胞為圓形且大小約為105奈米,包覆率為78%。 除此之外,在細胞攝取量、細胞毒性與細胞分佈等觀察,可發現接枝GE11的複合性奈米微胞皆有較佳之治療能力。在動物實驗中以非侵入式活體分子影像系統觀測複合型微胞在不同時間下於動物體內之累積量及分佈情形,實驗結果顯示接枝GE11的複合性奈米微胞相較之下有較多微胞累積在EGFR高表現之腫瘤組織位置並且同時具有較佳抑制腫瘤生長的能力。以上研究所得之結果,複合型奈米藥物微胞不論於細胞毒性研究或動物實驗均證實極具癌症治療效果。未來可運用於癌症光動力診斷及治療,達到抗癌效果,促進人類醫療福祉。 | zh_TW |
dc.description.abstract | Multifunctional theranostics have recently been intensively explored to optimize the efficacy and safety. Herein , we report multifunctional mixed micelle that constructed from graft copolymer PEGMA-co-DPA and diblock copolymer mPEG-b-PCL as the carrier of hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous photodynamic imaging and therapy. The functional inner core of PEGMA-co-DPA exhibited pH stimulate to accelerate drug release under slightly acidic microenvironments of tumors and the outer shell of mixed micelles with epidermal growth factor receptor (EGFR) – targeting GE11 peptides for active targeting of EGFR- overexpressing cancer cells. The results demonstrate that GE11-conjugated chlorin e6 – loaded mixed micelles with particle size around 100 nm and the mixed micelles had well defined core shell structure which was evaluated by TEM. From the in vitro cellular uptake studies, GE11-conjugated mixed micelles could effectively release chlorin e6 more than non- targeted mixed micelles, thereby providing a similar cytotoxic effect on the viability of HCT116 cancer cells (EGFR high expression) .
In vivo study revealed that specific targeting of GE11-conjugated mixed micelles exhibited cancer targeting and efficiency expression on tumor growth, indicating that GE11-conjugated chlorin e6 – loaded mixed micelles could be successfully applied to in vivo photodynamic tumor imaging and therapy simultaneously. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T00:06:29Z (GMT). No. of bitstreams: 1 ntu-102-R00548031-1.pdf: 3459336 bytes, checksum: b31de8b77315406f7cc492d250a8d1cc (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 口試委員會審定書 i
致謝 ii 中文摘要 iv ABSTRACT v CONTENTS vi LIST OF SCHEMES viii LIST OF TABLES ix LIST OF FIGURES x Chapter 1 Introduction 1 Chapter 2 Experiments procedure 4 2.1 Materials and equipment 5 2.2 Synthesis of PEGMA-co-DPA 5 2.3 Synthesis of m PEG-PCL 6 2.4 Synthesis of mal PEG-PCL 6 2.5 Potentiometric Titration Measurements 7 2.6 Preparation of Blank and Chlorin e6- loaded Nanoparticle 7 2.7 Preparation and Observation of GE11 conjugations 7 2.8 Characterization of Blank and Chlorin e6-loaded Nanoparticle 8 2.9 Detection of ROS 9 2.10 Differential Scanning Calorimetry (DSC) Measurement 10 2.11 Cell Culture 10 2.12 In vitro Cytotoxicity of Blank Nanoparticles 11 2.13 Cellular Uptake 11 2.14 Intracellular localization 12 2.15 In vitro Laser Induced PDT Efficiency 12 2.16 In vivo and ex vivo fluorescence imaging 13 2.17 In vivo photodynamic therapy 14 2.18 Necropsy and Immunohistochemical Analysis 14 2.19 Statistical Analysis 15 Chapter 3 Results and discussions 16 3.1 Synthesis and characterization of polymers 16 3.2 pH -responsive characterization of blank micelles 17 3.3 Characterization of chlorin e6 loaded micelles 18 3.4 Compositions of micelles 19 3.5 Optimization of ligand density on micelle suface 19 3.6 Cellular uptake and intracellular fluorescence generation of chlorin e6 loaded micelles 20 3.7 Intracellular localization of chlorin e6 loaded micelles 21 3.8 Cytotoxicity and phototoxicity 22 3.9 In vivo and ex vivo fluorescence imaging 23 3.10 In vivo photodynamic therapy and histology 24 Chapter 4 Conclusions 27 REFERENCE 28 SCHEME 34 TABLE 37 FIGURE 42 | |
dc.language.iso | en | |
dc.title | EGFR標靶型胜肽修飾於酸鹼應答性高分子微胞載體於光動力治療之應用 | zh_TW |
dc.title | EGFR-Targeting Peptide Conjugated pH-Sensitive Micelles as a Potential Drug Carrier for Photodynamic Therapy | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 駱俊良,賴秉杉,蕭仲凱 | |
dc.subject.keyword | 光動力治療,標靶治療,奈米藥物載體, | zh_TW |
dc.subject.keyword | photodynamic therapy,epidermal growth factor receptor,Chlorin e6,mixed micelle, | en |
dc.relation.page | 62 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2013-08-13 | |
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 |
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