以酸鹼響應嵌段共聚物做為Bcl-2小分子干擾核糖核酸及阿黴素二合一之載體來治療三陰性乳癌

簡易檢索 / 詳目顯示

回結果列表

研究生：	劉學文 Liu, Hsueh-Wen
論文名稱：	以酸鹼響應嵌段共聚物做為Bcl-2小分子干擾核糖核酸及阿黴素二合一之載體來治療三陰性乳癌 pH-Responsive Block Copolymer as a Bcl-2 siRNA and Doxorubicin Two-in-one Carrier for Triple-Negative Breast Cancer Therapy
指導教授：	彭之皓 Peng, Chi-How
口試委員:	陳俊太 Chen, Jiun-Tai 王潔 Wang, Jane
學位類別：	碩士 Master
系所名稱：	理學院 - 化學系 Department of Chemistry
論文出版年：	2019
畢業學年度：	108
語文別：	中文
論文頁數：	131
中文關鍵詞：	高分子微胞、酸鹼響應、阿黴素、Bcl-2小分子干擾核糖核酸、協同效應
外文關鍵詞：	Nanoparticles, pH response, DOX, Bcl-2 siRNA, Synergistic Effect
相關次數：	點閱：3 下載：0
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

　結合化學治療和基因治療，使其於癌症治療中產生協同效應達到誘導增強治療的功效，為了實現這一目標本研究設計不同長度之三嵌段共聚物PEG-b-PDMAEMA-b-PDPA與隨機共聚物PEG-b-(PDMAEMA-r-PDPA)，用於將阿黴素（DOX）和Bcl-2小分子干擾核糖核酸（siRNA）靶向同時遞送到三陰性乳癌細胞中。探討其自組裝構型差異與不同鏈長之共聚物，對於藥物載送效果的影響，以及探討共同負載之兩種藥物間的協同效應。由實驗結果得知，三嵌段共聚物具有較佳的藥物包覆能力，而其中具有最長PDMAEMA鏈段之共聚物PEG113-b-PDMAEMA55-b-PDPA59（LB）有著最佳的載送效果。PEG113-b-PDMAEMA55-b-PDPA59（LB）之阿黴素包覆效率能夠達到80%，於pH= 7.4與5.0的環境下分別進行體外釋放，24小時阿黴素之累積釋放率分別達到24%與 68%，而若延長至96小時，則可達40%與接近100%的累積釋放率。而在氮磷比為20的條件下，PEG113-b-PDMAEMA55-b-PDPA59（LB）負載小分子干擾核糖核酸之包覆效率能高達94%，使其於pH= 7.4與5.0的環境下釋放了24小時後，其累積釋放率分別為14.6%與59%，由以上實驗之差距可以得知，PEG113-b-PDMAEMA55-b-PDPA59（LB）奈米載體具有相當靈敏之酸鹼響應。重要的是，於三陰性乳癌細胞（MDA-MB-231）之細胞活性實驗中，PEG113-b-PDMAEMA55-b-PDPA59（LB）載體包覆Bcl-2小分子干擾核糖核酸以及阿黴素之毒殺效果，比只包覆阿黴素之載體多出了約20%，證實兩者藥物有顯著的協同效應，也證實PEG113-b-PDMAEMA55-b-PDPA59（LB）微胞能夠成功地將雙藥負載運送至細胞中。期許未來能夠提供作為結合基因治療與化療藥物之複合治療載體平台，並用於三陰性乳癌的靶向治療，對治療方面有所貢獻。

The combination of chemotherapy and gene therapy is known to induce the enhanced therapeutic efficacy in the cancer therapy, which is called synergistic effect. In this study, triblock copolymer（PEG-b-PDMAEMA-b-PDPA）and random copolymer（PEG-b-(PDMAEMA-r-PDPA)）with different composition has been designed as the co-delivery platforms, which targeted simultaneous delivery of doxorubicin (DOX) and Bcl-2 small interfering RNA (siRNA) into breast cancer cells. The efficiency of drug encapsulation was optimized by changing the chain length, composition and self-assembled configuration of copolymer. The experimental results show that the triblock copolymer has better drug-carrying capacity than the random copolymer. The copolymer PEG113-b-PDMAEMA55-b-PDPA59（LB） with the longest PDMAEMA segment is the best carrier. The drug loading efficiency of DOX could achieve around 80%, and the condensation efficiency of siRNA was 94% under N/P = 20. Co-loading of Bcl-2 siRNA and DOX wouldn't affect the high carry efficiency. In vitro drug cumulative release rate of DOX was 40% and nearly 100% at the environment of pH=7.4 and 5.0 in 96 hrs. In 24 hours, the cumulative release rate of siRNA could reach 14.6% and 59% in the environment of pH=7.4 and 5.0. The significant difference between the two environments demonstrated that these nanoparticles have a very sensitive pH response. And it could be used as a good platform for the combination of chemotherapy and gene therapy.
Importantly, by the results of cell viability, the codelivery of Bcl-2 siRNA and DOX showed significantly enhanced toxicity in MDA-MB-231 breast cancer cells around 20% more than the codelivery of control siRNA and DOX in 50 nM of siRNA. Therefore, a significant synergistic effect between Bcl-2 siRNA and DOX has been observed. PEG113-b-PDMAEMA55-b-PDPA59（LB） micelles thus confirmed to be able to carry the dual drug into the cells. These results indicate DOX/Bcl-2 siRNA co-delivery system by PEG113-b-PDMAEMA55-b-PDPA59（LB） is promising for targeted treatment of breast cancer.

摘要    I
Abstract    III
謝誌    V
目錄    VI
圖目錄    X
表目錄    XIII
式目錄    XIV
第一章    　文獻回顧    1
1-1  癌症（Cancer）    1
1-1-1  乳癌    3
1-2  常見治療乳癌之方式    4
1-2-1  手術治療    4
1-2-2  放射治療    4
1-2-3  化學治療    5
1-2-4  荷爾蒙治療    7
1-3  基因型藥物治療癌症（Gene-based Therapeutics）    8
1-3-1  質體去氧核糖核酸（plasmid DNA, pDNA）    8
1-3-2  小分子干擾核糖核酸（small-interfering RNA, siRNA）與微型核糖核酸（microRNA, miRNA）    9
1-4  奈米載體應用以治療癌症    12
1-4-1  增強通透與滯留效應（Enhanced Permeability and Retention Effect, EPR）    12
1-4-2  腫瘤微環境（Tumor Microenvironment）    14
1-4-3  核內體逃脫（Endosomal Escape）    15
1-5  刺激響應型高分子奈米載體（Stimuli-Responsive Polymeric Nanocarrier）    18
1-5-1  酸鹼響應型高分子微胞奈米載體（pH-Responsive Polymeric Nanocarrier）    19
1-5-2  氧化還原響應型高分子奈米載體（Redox-Responsive Polymeric Nanocarrier）    21
1-5-3  其他響應型高分子微胞奈米載體（Other Responsive Polymeric Nanocarriers）    22
1-6  多功能小分子2,3-二溴馬來醯亞胺（2,3-Dibromomaleimide, DBM）    24
1-6-1  可逆反應之高選擇性    24
1-6-2  功能性修飾（螢光修飾以及高分子修飾）    25
1-7  原子轉移自由基聚合反應（Atom Transfer Radical Polymerization, ATRP）    29
1-8  研究動機    33
第二章    酸鹼響應之二合一奈米藥物平台其基因與化療藥物之材料與實驗方法    35
2-1  材料設計    35
2-2  三嵌段共聚物與隨機共聚物之合成與鑑定    36
2-2-1 聚乙烯醇引發劑（PEG-Br）之合成    36
2-2-2  Poly（ethylene glycol）-b-poly（2-（dimethylamino）ethyl methacrylate）-b-poly（2-（diisopropylamino）ethyl methacrylate）（PEG-b-PDMAEMA-b-PDPA）三嵌段共聚物之聚合反應    37
2-2-3  Poly（ethylene glycol）-b-（poly（2-（dimethylamino）ethyl methacrylate）-r-poly（2-（diisopropylamino）ethyl methacrylate））（PEG-b-(PDMAEMA-r-PDPA)）隨機共聚物之聚合反應    39
2-3  三嵌段共聚物與隨機共聚物之材料特性及刺激響應分析    41
2-3-1  高分子之臨界微胞濃度（Critical Micelle Concentration, CMC）    41
2-3-2  高分子之酸鹼性質滴定    41
2-3-3  高分子對酸鹼值之靈敏度測定    41
2-3-4  高分子奈米微胞製程    41
2-3-5  高分子奈米微胞粒徑分析    42
2-3-6  高分子奈米微胞酸鹼響應分析    43
2-3-7 高分子奈米微胞表面電位量測    43
2-4  三嵌段共聚物與隨機共聚物之阿黴素包覆及釋放    44
2-4-1  製備包覆阿黴素之高分子奈米微胞與分析    44
2-4-2  包覆阿黴素之高分子微胞前後之螢光強度    46
2-4-3  製作阿黴素於不同pH磷酸緩衝液之減量線    46
2-4-4  包覆阿黴素之高分子奈米微胞在酸鹼響應下之釋放    46
2-5  小分子干擾核糖核酸之高分子複合體製備與釋放情形    48
2-5-1 小分子干擾核糖核酸之微胞複合體製備與分析    48
2-5-2 微胞複合體釋放在酸鹼響應下之釋放    48
2-6  細胞實驗分析    50
2-6-1  基因沉默（gene silencing）    50
2-6-2  細胞存活率（viability）    51
2-6-3  細胞吞噬實驗（uptake experiment）    52
第三章    酸鹼響應之二合一奈米藥物平台其基因與化療藥物之結果與探討    53
3-1  三嵌段共聚物與隨機共聚物合成    53
3-2  三嵌段共聚物與隨機共聚物之材料特性與刺激響應分析    55
3-2-1  高分子之臨界微胞濃度（Critical Micelle Concentration, CMC）    55
3-2-2  高分子之酸鹼性質    57
3-2-3  高分子奈米微胞對於酸鹼性變化之靈敏度    59
3-3  三嵌段共聚物與隨機共聚物奈米微胞之粒徑分析與刺激響應分析    61
3-3-1 高分子奈米微胞粒徑大小與表面電位    61
3-3-2 高分子奈米微胞之穩定性    62
3-4  以三嵌段共聚物與隨機共聚物形成奈米微胞攜帶阿黴素    64
3-4-1  包覆阿黴素之高分子奈米微胞製備以及負載效率之計算    64
3-4-2  包覆阿黴素之高分子微胞前後粒徑大小與螢光強度    66
3-5  小分子干擾核糖核酸之高分子微胞複合體（polyplexes）之包覆效率    69
3-6  以包覆效率最佳之材料PEG113-b-PDMAEMA55-b-PDPA59（LB）共同負載阿黴素與小分子干擾核糖核酸    72
3-6-1  PEG113-b-PDMAEMA55-b-PDPA59（LB）高分子奈米微胞粒徑之酸鹼影響    72
3-6-2    PEG113-b-PDMAEMA55-b-PDPA59（LB）包覆阿黴素於不同酸鹼下釋放情形    74
3-6-3  PEG113-b-PDMAEMA55-b-PDPA59（LB）之小分子干擾核糖核酸微胞複合體於不同酸鹼值下之釋放情形    76
3-6-4    PEG113-b-PDMAEMA55-b-PDPA59（LB）共同負載阿黴素與小分子干擾核糖核酸之微胞複合體粒徑大小與表面電位分析    78
3-7 以PEG113-b-PDMAEMA55-b-PDPA59（LB）載負阿黴素與小分子干擾核糖核酸之細胞分析    79
3-7-1  基因沉默（gene silencing）    79
3-7-2  細胞存活率（viability）    81
3-7-3  細胞吞噬實驗（uptake experiment）    84
3-8  結論    86
第四章    具馬來醯亞胺核心之還原與酸鹼響應的高分子液胞用於藥物控制釋放    88
4-1  實驗設計    88
4-2  實驗過程中之問題與解決方式    90
4-2-1  溶劑對化合物之影響與解決方法    91
4-2-2  還原劑效果與解決方法    94
4-2-3  鍵擊反應之產物的鑑定方式    96
4-2-4  立體障礙結構之影響與解決方法    97
4-3  AB2-type雙嵌段共聚物之合成與鑑定    99
4-3-1   聚乙二醇甲醚-疊氮化物（PEG113-N3）之合成59    99
4-3-2   N-propargyl-2,3-dibromomaleimide 之合成48    100
4-3-3   3,4-bis((2-hydroxyethyl)thio)-1-(propynyl)pyrroledione,  alkyne-DTM- (SCH2CH2OH)2 之合成    101
4-3-4   PEG113-Mal-（SCH2CH2OH）2藉由鍵擊反應之合成    102
4-3-5   PEG113-Mal-（SCH2CH2OBiBB）2之巨雙頭起始劑合成步驟    103
4-3-6   PEG113-Mal-（PDPA30）2之合成步驟    105
4-4   結論與未來展望    107
藥品與儀器    108
參考文獻    112
附錄    122


                                

1. Gilman, A. The Initial Clinical Trial of Nitrogen Mustard. Am. J. Surg. 1963, 105, 574-578.
2. Farber, S.; Diamond, L.; Mercer, R.; Sylvester, R.; Wolff, J. Temporary Remissions in Acute Leukemia in Children Produced by Folic Acid Antagonist, 4-Aminopteroyl-Glutamic Acid (Aminopterin) New. Engl. J. Med. 1948, 238, 787-793.
3. Nitiss, J. Targeting DNA Topoisomerase II in Cancer Chemotherapy. Nat. Rev. Cancer 2009, 9, 338-350.
4. Zhu, H.; Sarkar, S.; Scott, L.; Danelisen, I.; Trush, M.; Jia, Z.; Li, R. Doxorubicin Redox Biology: Redox Cycling, Topoisomerase Inhibition, and Oxidative Stress. Reactive Oxygen Species 2016, 1, 189-198.
5. Morrison, B.; Morris, J.; Steel, J. Lung Cancer-Initiating Cells: A Novel Target for Cancer Therapy. Target Oncol. 2013, 8, 159-172.
6. Bou-Assaly, W.; Mukherji, S. Cetuximab (Erbitux) Am. J. Neuroradiol. 2010, 31, 626-627.
7. Luo D.; Saltzman WM. Synthetic DNA delivery systems. Nat. Biotechnol. 2000, 18, 33–37.
8. Hamilton AJ.; Baulcombe DC. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 1999, 286, 950–952.
9. Meister G.; Tuschl T. Mechanisms of gene silencing by double-stranded RNA. Nature 2004, 431, 343-349
10 Pritchard CC.; Cheng HH.; Tewari M. MicroRNA profiling: approaches and considerations. Nat. Rev. Genet. 2012, 13, 358–369.
11. Matsumura, Y.; Maeda, H. A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs. Cancer Res. 1986, 46, 6387-6392.
12. Peer, D.; Karp, J.; Hong, S.; Farokhzad, O.; Margalit, R.; Langer, R. Nanocarriers as an Emerging Platform for Cancer Therapy. Nat. Nanotechnol. 2007, 2, 751-760.
13. Gatenby, R.; Gillies, R. Why Do Cancers Have High Aerobic Glycolysis? Nat. Rev. Cancer 2004, 4, 891-899.
14. Cheng, R.; Meng, F.; Deng, C.; Zhong, Z. Bioresponsive Polymeric Nanotherapeutics for Targeted Cancer Chemotherapy. Nano Today 2015, 10, 656-670.
15. Low, P.; Henne, W.; Doorneweerd, D. Discovery and Development of Folic-Acid-Based Receptor Targeting for Imaging and Therapy of Cancer and Inflammatory Diseases. Acc. Chem. Res. 2008, 41, 120-129.
16. Trachootham, D.; Alexandre, J.; Huang, P. Targeting Cancer Cells by ROS-Mediated Mechanisms: A Radical Therapeutic Approach? Nat. Rev. Drug Discovery 2009, 8, 579-591.
17. Varkouhi, A.; Scholte, M.; Storm, G.; Haisma, H. Endosomal Escape Pathways for Delivery of Biologicals. J. Controlled Release 2011, 151, 220-228.
18. Li, W.; Nicol, F.; Szoka, F. GALA: A Designed Synthetic pH-Responsive Amphipathic Peptide with Applications in Drug and Gene Delivery. Adv. Drug Deliverery Rev. 2004, 56, 967-985.
19. Zelphati; Szoka Mechanism of Oligonucleotide Release from Cationic Liposomes. Proc. Natl. Acad. Sci. 1996, 93, 11493-11498.
20. Pack, D.; Hoffman, A.; Pun, S.; Stayton, P. Design and Development of Polymers for Gene Delivery. Nat. Rev. Drug Discovery 2005, 4, 581-593.
21. Cabral, H.; Nakanishi, M.; Kumagai, M.; Jang, W.-D.; Nishiyama, N.; Kataoka, K. A Photo-Activated Targeting Chemotherapy Using Glutathione Sensitive Camptothecin-Loaded Polymeric Micelles. Pharm. Res. 2009, 26, 82-92.
22. El-Sayed, A.; Futaki, S.; Harashima, H. Delivery of Macromolecules Using Arginine-Rich Cell-Penetrating Peptides: Ways to Overcome Endosomal Entrapment. AAPS. J. 2009, 11, 13-22.
23. Zhang, L.; Eisenberg, A. Multiple Morphologies of “Crew-Cut” Aggregates of Polystyrene-b-Poly(acrylic Acid) Block Copolymers. Science 1995, 268, 1728-1731.
24. Torchilin, V. Recent Advances with Liposomes as Pharmaceutical Carriers. Nat. Rev. Drug Discovery 2005, 4, 145-160.
25. Discher, D.; Ahmed, F. Polymersomes. Annu. Rev. Biomed. Eng. 2006, 8, 323-341.
26. Harris, M.; Chess, R. Effect of Pegylation on Pharmaceuticals. Nat. Rev. Drug Discovery 2003, 2, 214-221.
27. Li, S.; Meng, F.; Wang, Z.; Zhong, Y.; Zheng, M.; Liu, H.; Zhong, Z. Biodegradable Polymersomes with an Ionizable Membrane: Facile Preparation, Superior Protein Loading, and Endosomal pH-Responsive Protein Release. Eur. J. Pharm. Biopharm. 2012, 82, 103-111.
28. Du, Y.; Chen, W.; Zheng, M.; Meng, F.; Zhong, Z. pH-Sensitive Degradable Chimaeric Polymersomes for the Intracellular Release of Doxorubicin Hydrochloride. Biomaterials 2012, 33, 7291-7299.
29. Wang, L.; Liu, G.; Wang, X.; Hu, J.; Zhang, G.; Liu, S. Acid-Disintegratable Polymersomes of pH-Responsive Amphiphilic Diblock Copolymers for Intracellular Drug Delivery. Macromolecules 2015, 48, 7262-7272.
30. Pearson, R.; Warren, N.; Lewis, A.; Armes, S.; Battaglia, G. Effect of pH and Temperature on PMPC–PDPA Copolymer Self-Assembly. Macromolecules 2013, 46, 1400-1407.
31. Massignani, M.; Canton, I.; Sun, T.; Hearnden, V.; MacNeil, S.; Blanazs, A.; Armes, S.; Lewis, A.; Battaglia, G. Enhanced Fluorescence Imaging of Live Cells by Effective Cytosolic Delivery of Probes. PLos One 2010, 5, e10459.
32. Sun, H.; Guo, B.; Li, X.; Cheng, R.; Meng, F.; Liu, H.; Zhong, Z. Shell-Sheddable Micelles Based on Dextran-SS-Poly(epsilon-Caprolactone) Diblock Copolymer for Efficient Intracellular Release of Doxorubicin. Biomacromolecules 2010, 11, 848-854.
33. Chen, W.-H.; Luo, G.-F.; Lei, Q.; Jia, H.-Z.; Hong, S.; Wang, Q.-R.; Zhuo, R.-X.; Zhang, X.-Z. MMP-2 Responsive Polymeric Micelles for Cancer-Targeted Intracellular Drug Delivery. Chem. Commun. 2014, 51, 465-468.
34. Zhao, X.; Qi, M.; Liang, S.; Tian, K.; Zhou, T.; Jia, X.; Li, J.; Liu, P. Synthesis of Photo- and pH Dual-Sensitive Amphiphilic Copolymer PEG43-b-P(AA76-co-NBA35-co-tBA9) and Its Micellization as Leakage-Free Drug Delivery System for UV-Triggered Intracellular Delivery of Doxorubicin. ACS Appl. Mater. Interfaces 2016, 8, 22127-22134.
35. Schelté; Boeckler, C.; Frisch, B.; Schuber, F. Differential Reactivity of Maleimide and Bromoacetyl Functions with Thiols: Application to the Preparation of Liposomal Diepitope Constructs. Bioconjugate Chem. 2000, 11, 118-123.
36. Vanderhooft, J.; Mann, B.; Prestwich, G. Synthesis and Characterization of Novel Thiol-Reactive Poly(ethylene Glycol) Cross-Linkers for Extracellular-Matrix-Mimetic Biomaterials. Biomacromolecules 2007, 8, 2883-2889.
37. Mather, B.; Viswanathan, K.; Miller, K.; Long, T. Michael Addition Reactions in Macromolecular Design for Emerging Technologies. Prog. Polym. Sci. 2006, 31, 487-531.
38. Youziel, J.; Akhbar, A.; Aziz, Q.; Smith, M.; Caddick, S.; Tinker, A.; Baker, J. Bromo- and Thiomaleimides as a New Class of Thiol-Mediated Fluorescence “turn-On” Reagents. Org. Biomol. Chem. 2013, 12, 557-560.
39. Saito, G.; Swanson, J.; Lee, K.-D. Drug Delivery Strategy Utilizing Conjugation via Reversible Disulfide Linkages: Role and Site of Cellular Reducing Activities. Adv. Drug Deliverery Rev. 2003, 55, 199-215.
40. Güçlü, K.; Özyürek, M.; Güngör, N.; Baki, S.; Apak, R. Selective Optical Sensing of Biothiols with Ellman’s Reagent: 5,5′-Dithio-bis(2-Nitrobenzoic Acid)-Modified Gold Nanoparticles. Anal. Chim. Acta 2013, 794, 90-98.
41. Smith, M.; Schumacher, F.; Ryan, C.; Tedaldi, L.; Papaioannou, D.; Waksman, G.; Caddick, S.; Baker, J. Protein Modification, Bioconjugation, and Disulfide Bridging Using Bromomaleimides. J. Am. Chem. Soc. 2010, 132, 1960-1965.
42. Mabire, A.; Robin, M.; Quan, W.-D.; Willcock, H.; Stavros, V.; O’Reilly, R. Aminomaleimide Fluorophores: A Simple Functional Group with Bright, Solvent Dependent Emission. Chem. Commun. 2015, 51, 9733-9736.
43. Robin, M. P.; Wilson, P.; Mabire, A.; Kiviaho, J.; Raymond, J.; Haddleton, D.; O’Reilly, R. Conjugation-Induced Fluorescent Labeling of Proteins and Polymers Using Dithiomaleimides. J. Am. Chem. Soc. 2013, 135, 2875-2878.
44. Liang, L.; Astruc, D. The copper(I)-Catalyzed Alkyne-Azide Cycloaddition (CuAAC) “click” Reaction and Its Applications. An Overview. Coord. Chem. Rev. 2011, 255, 2933-2945.
45. Jones, M.; Strickland, R.; Schumacher, F.; Caddick, S.; Baker, J.; Gibson, M.; Haddleton, D. Highly Efficient Disulfide Bridging Polymers for Bioconjugates from Radical-Compatible Dithiophenol Maleimides. Chem. Commun. 2012, 48, 4064-4066.
46. Matyjaszewski, K.; Spanswick, J. Controlled/living Radical Polymerization. Materials Today 2005, 8, 26-33.
47. Robin, M.; Jones, M.; Haddleton, D.; O’Reilly, R. Dibromomaleimide End Functional Polymers by RAFT Polymerization Without the Need of Protecting Groups. ACS Macro Lett. 2012, 1, 222-226.
48. Wang, H.; Xu, M.; Xiong, M.; Cheng, J. Reduction-Responsive Dithiomaleimide-Based Nanomedicine with High Drug Loading and FRET-Indicated Drug Release. Chem. Commun. 2015, 51, 4807-4810.
49. Kato, M.; Kamigaito, M.; Sawamoto, M.; Higashimura, T. Polymerization of Methyl Methacrylate with the Carbon Tetrachloride/Dichlorotris- (triphenylphosphine)ruthenium(II)/Methylaluminum Bis(2,6-Di-Tert-Butylphenoxide) Initiating System: Possibility of Living Radical Polymerization. Macromolecules 1995, 28, 1721-1723.
50. Tang, W.; Tsarevsky, N.; Matyjaszewski, K. Determination of Equilibrium Constants for Atom Transfer Radical Polymerization. J. Am. Chem. Soc. 2006, 128, 1598-604.
51. Tang, W.; Kwak, Y.; Braunecker, W.; Tsarevsky, N.; Coote, M.; Matyjaszewski, K. Understanding Atom Transfer Radical Polymerization: Effect of Ligand and Initiator Structures on the Equilibrium Constants. J. Am. Chem. Soc. 2008, 130, 10702-10713.
52. Matyjaszewski, K.; Tsarevsky, N. Nanostructured Functional Materials Prepared by Atom Transfer Radical Polymerization. Nat. Chem. 2009, 1, 276-288.
53. Mabire, A.; Robin, M.; Willcock, H.; Pitto-Barry, A.; Kirby, N.; O’Reilly, R. Dual Effect of Thiol Addition on Fluorescent Polymeric Micelles: ON-to-OFF Emissive Switch and Morphology Transition. Chem. Commun. 2014, 50, 11492-11495.
54. Jens Gaitzsch.; Vijay Chudasama.; Eloise Morecroft.; Lea Messager.; Giuseppe Battaglia. Synthesis of an Amphiphilic Miktoarm Star Terpolymer for Self-Assembly into Patchy Polymersomes. ACS Macro Lett. 2016, 5, 351−354
55. James-Kevin Y.; Tan, Jennifer L.; Choi, Hua Wei.; Joan G. Schellinger.; Suzie H.; Pun. Biomater. Reducible, dibromomaleimide-linked polymers for gene delivery. Sci., 2015, 3, 112–120
56. Mathew W. Jones.; Rachel A. Strickland.; Felix F. Schumacher.; Stephen Caddick, James.; R. Baker, Matthew I.; Gibson.; David M. Haddleton. Polymeric Dibromomaleimides As Extremely Efficient Disulfide Bridging Bioconjugation and Pegylation Agents. J. Am. Chem. Soc. 2012, 134, 1847−1852
57. Hua Wang.; Ming Xu.; Menghua Xionga.; Jianjun Cheng. Reduction-responsive dithiomaleimide-based nanomedicine with high drug loading and FRET-indicated drug release. Chem. Commun., 2015, 51, 4807−4810
58. Marc Karman.; Ester Verde-Sesto.; Christoph Weder.; and Yoan C. Simon. Mechanochemical Fluorescence Switching in Polymers Containing Dithiomaleimide ACS Macro Lett. 2018, 7, 1099−1104
59. König, H.; Gorelik, T.; Kolb, U.; Kilbinger, A. Supramolecular PEG-co-Oligo(p-Benzamide)s Prepared on a Peptide Synthesizer. J. Am. Chem. Soc. 2007, 129, 704-708.
60. Jones, M.; Strickland, R.; Schumacher, F.; Caddick, S.; Baker, J.; Gibson, M.; Haddleton, D. Polymeric Dibromomaleimides As Extremely Efficient Disulfide Bridging Bioconjugation and Pegylation Agents. J. Am. Chem. Soc. 2012, 134, 1847-1852.

全文公開日期 2024/09/17 (校內網路)
全文公開日期本全文未授權公開 (校外網路)
全文公開日期本全文未授權公開 (國家圖書館：臺灣博碩士論文系統)

簡易檢索 / 詳目顯示

相關論文