聚(氮-異丙基丙烯醯胺)/聚乙烯醇衍生酸鹼/磁/熱敏感型奈米藥物載體於刺激藥物釋放之研究

郭志宇

doi:10.6342/NTU201603755

山西大学，您好！

感谢采购，人社期刊库｜人社论文库，期间：2024/01/01~2024/12/31

感谢试用，科学期刊库｜科学论文库，期间：2024/10/20~2025/01/20

浏览高级检索

关闭
检索检索高级检索出版物检索
浏览期刊主题浏览核心期刊浏览期刊拼音浏览

关闭

查询符号(半角)	查询符号意义说明
空格	表示为「AND」两个查询词之交集
双引号 ( " " )	片语以双引号标示开始及结束，而且只寻找出现顺序相同的字词，例： " image process "
?	表示一个字母切截，输入两个?表两个字母，依此类推，例：输入「Appl?」，查得结果应为appl e , appl y … ( 常用于英文字查询 )
*	表示不限字母切截，由0~n. 例：输入「appl*」，查得结果应为appl e , appl es , appl y , appl ied , appl ication … ( 常用于英文字查询 )
AND、OR、NOT	布尔逻辑组合关键字，用来扩大或缩小查询范围的技巧。 (1) AND ：缩小查询范围 (2) OR ：扩大查询范围(3) NOT：排除不相关的范围

DOI 是数位物件识别码（ D igital O bject I dentifier ）的简称，
为物件在网路上的唯一识别码，可用于永久连结并引用目标物件。

使用DOI作为永久连结

每个DOI号前面加上「 http://dx.doi.org/ 」便成为永久网址。
如以DOI号为 10.5297/ser.1201.002 的文献为例，此文献的永久连结便是： http://dx.doi.org/ 10.5297/ser.1201.002 。
日后不论出版单位如何更动此文献位置，永久连结所指向的位置皆会即时更新，不再错失重要的研究。

引用含有DOI的文献

有DOI的文献在引用时皆应同时引用DOI。若使用APA、Chicago以外未规范DOI的引用格式，可引用DOI永久连结。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。

书目管理工具

相关连结

问题回报

全文下载

聚(氮-异丙基丙烯醯胺)/聚乙烯醇衍生酸硷/磁/热敏感型奈米药物载体於刺激药物释放之研究

Poly(N-isopropylacrylamide)/Poly(vinyl alcohol) Related pH/magnetic/thermo induced Nanocarriers for Stimuli-triggered Release

郭志宇 , 博士　　导师：邱文英　　共同指导教授：刘定宇

英文 DOI： 10.6342/NTU201603755

聚(氮-异丙基丙烯醯胺) ；可逆性分裂加成链转移活性聚合法；自组装；刺激诱发之药物释放；热治疗；标靶式治疗；姜黄素； Poly(N-isopropylacrylamide) ； reversible addition-fragmentation chain transfer (RAFT) polymerization ； self-assembly ； stimuli-triggered release ； hyperthermia ； targeting therapy ； curcumin

0 个人觉得这篇文章赞

摘要 │ 参考文献 (237) │ 国际计量

摘要〈TOP〉

本研究的目的旨在设计以及制备以聚(氮-异丙基丙烯醯胺)，Poly(N-isopropylacrylamide) 或聚乙烯醇，Poly(vinyl alcohol)为主体之衍生酸硷/磁/热感应性高分子及其复合材料，并探讨此复合材料作为肿瘤组织的医疗平台之适用性，以及是否能够提供新颖及有效的诊断和治疗。
本论文主文共分为三大部份。第一部份以可逆性分裂加成链转移活性聚合法合成(Reversible Addition-Fragmentation chain Transfer polymerization, RAFT polymerization) 聚(氮-异丙基丙烯醯胺)以及聚(异丙基丙烯醯胺-丙烯酸)之嵌段共聚合物。第二部份将以第一部分所合成之嵌段共聚合物为主体，制备多功能性药物载体，并透过体外及生物试验获得其生物医学之性质。第三部份引入多重乳化法(double-emulsion)并以聚乙烯醇(Polyvinyl alcohol, PVA)为主体，制备具磁性之核壳型(core-shell)药物载体。
第一部份挑选(S,S'-bis(a,a'-dimethyl-a"-acetic acid)trithiocarbonate, CMP)做为可逆性分裂加成链转移活性聚合法(RAFT polymerization)之链转移剂(chain transfer agent, CTA)。引入热裂解型起始剂(azobisisobutyronitrile, AIBN)以及使用有机溶剂(methanol)於70度下反应後，可以制备出ABA三嵌段型高分子(poly(acrylic acid-block-N-isopropylacrylamide-block-acrylica acid), poly(AA-b-NIPAAm-b-AA)并能将准确的控制嵌段型高分子链段上NIPAAm与AA的链段比例。藉由改变不同的高分子链段比例、溶液酸硷度、操作温度、浓度等，观察对於高分子自组装的型态以及其物理性质之影响。
第二部份包含第三及第四章。第三章引入经表面改质过之磁性氧化铁，结合自组装後之高分子水胶，制备出具磁性控制、酸硷、温度感应型之药物载体，并探讨其药物释放之行为。第四章则是延续第三章之研究，将具备癌症细胞辨识性之标靶分子—叶酸(Folic acid)接枝於磁性药物载体表面，同时也引入疏水型抗癌药物—姜黄素(Curcumin)，制备出同时具有远端操作(磁性控制)、温度感应、标靶治疗之药物载体，并探讨此药物载体对於人体乳癌细胞株(MCF-7 cell line)之细胞选择性以及毒杀效果。
第三部份则以第六章为主。以聚乙烯醇为主体，利用多重乳化法备制核壳型磁性药物载体。实验结果显示此药物载体对於抗癌药物承载具有相当大之相容性，无论亲、疏水型小分子药物，胜肽型(peptide)巨分子药物都能被稳定的包覆。接枝标靶分子(atherosclerotic plaque-specific peptide-1, AP-1)後，此药物载体在细胞毒性测试中，也充分表现出对於小鼠直肠大肠癌细胞株(Mouse colon carcinoma cell line, CT26)的辨识能力。随後进行动物实验，对於刻意诱发之小鼠肿瘤组织进行磁性药物载体之直接注射治疗，发现在高周波磁场作用下不仅能够抑制肿瘤组织的生长，磁性粒子所产生之高热也同时能提供对肿瘤组织的热治疗。
附录第一部分中藉由控制特定的温度以及酸硷值，将已自组装後的远嵌型高分子核壳奈米颗粒应用於药物控制释放系统。引入具有萤光特性之小分子(Rhodamine 6G, R6G)於此药物载体之表面及内部後，探讨在不同的环境及浓度下此萤光标签型药物载体之控制释放行为。第二部份则收录了利用脂类自组装而形成的奈米圆盘，在引入具有酸降解性的双胺(acid-degradable diamine)後，则可以制备出对癌症细胞感应型的药物载体，并对此载体的物理、化学性质进行探讨。至於附录的第三部分则是使用高温乳化法在以聚(氮-异丙基丙烯醯胺)为基质的水胶中引入磁性氧化铁颗粒，并利用无电镀法制备具有催化效果之铂奈米粒子，未来此磁性催化复合材料应用时，便可以利用磁性来进行复材之控制及回收。

并列摘要〈TOP〉

In this research, Poly(vinyl alcohol)- and Poly(N-isopropylacrylamide) based copolymers and their pharmatical composites were prepared as the medical platform with pH/magnetic/thermo properties for providing the novel and effective diagnosis and treatment toward tumor tissues. Three divided sections were contained in this thesis. In the first section, reversible addition-fragmentation chain transfer (RAFT) polymerization was performed and applied to synthesize ABA tri-block copolymers via living polymerization. In the second section, we fabricated several kinds of multi-functional nanomedicines as the extended employments of the as-synthesized block copolymers. Besides, their biomedical properties of nanomedicines were also obtained with in vitro and in vivo tests. In the third section, double-emulsion method was conducted for core-shell, PVA-based nanoparticles as well as the anti-cancer drugs’ encapsulation. Additionally, acid-cleavable, nanodiscs-based nanoscaffold was designed and prepared via EDC/NHS initiated crosslinking between the synthesized acid-degradable diamines and PEGylated nanodiscs. Platinum and Fe3O4 core-shell nanoparticles were designed and constructed by temperature-induced emulsion of the poly(N-isopropylacrylamide) following with electroless plating methods. The results were both shown in the appendix section.
Chapter 2 was contained in the first section and RAFT polymerization with S,S'-bis(a,a'-dimethyl-a"-acetic acid)trithiocarbonate (CMP) as the chain transfer agent (CTA) were demonstrated. By using the thermal initiation following with the RAFT polymerization in methanol, ABA tri-block copolymers, poly(acrylic acid-block-N-isopropylacrylamide-block-acrylic acid), poly(AA-b-NIPAAm-b-AA) with precise control of the main chain composition to the repeating monomer units were prepared. Moreover, further discussions were studied toward the morphology and physical property changes resulting from the different composition ratio of NIPAAm to AA ratio and the system conditions involving pH values and temperatures. Various shapes of poly(AA-b-NIPAAm-b-AA)-based, self-assembly nanoparticles including core-shell nanoparticle, physical crosslinked nanogel, and inversed physically crosslinked nanogel formed at specific conditions. To the best of our knowledge, this was the first research that focus on the relationship between chemical structure and physical properties of poly(AA-b-NIPAAm-b-AA) tri-block copolymers systemically.
The second section includes Chapter 3 and Chapter 4, in which different nanocarriers were fabricated and studied for bio-medical applications. In Chapter 3, physically crosslinked nanogels were employed into the preparation of anti-cancer nanomedicine. Magnetic iron oxide (Fe3O4) was introduced to achieve the remote control as well as the stability of magnetic nanocarriers. Furthermore, the intelligent functionality of nanocarriers was realized resulting from highly pH- and magnetically- sensitive quality because of the iron oxides and the functional groups (-COOH and -NH2) on its surface. Chapter 4 contains the following work related of Chapter 3, in which we further modified the magnetic nanocarriers with folic acid to gain the cancer cell-selectivity and replaced the model drug into the hydrophobic one, curcumin. Various release and pharmatical parameters such as biocompatibility, cytotoxicity, cell selectivity, and release behaviors were studied. 
Chapter 5 was contained in the third section where we paid more attention to develop another way of nanocarriers’ preparation including double-emulsion, sol-gel reaction, and following with targeting ligand immobilization. Both in vitro and in vivo experiments were brought out to give a full scope of pharmatical applications of the magnetic nanocarriers toward tumor therapy. 
In Appendix 1, we prepared the thermo- and pH-sensitive, fluorescent-labeled nanocarriers with two kinds of drug-loading process. Rhodamine 6G, a fluorescent dye, was used as the modeling drugs not only to demonstrate the release behavior but also for maintaining the spherical structure of self-assembled telechelic HOOC-PNIPAAm-COOH homopolymers. In Appendix 2, PEGylated lipids were mixed with long-chain and short-chain lipids to form carboxylic acids-exposed nanodiscs (a-discs). An acid-degradable diamine was synthesized and applied for stringing the nanodisc in order to enlarge their size for preventing the un-desired cellular uptake and providing controlled release as an anti-cancer platform. Attentions were concentrated on acquiring a stable, well-dispersed Fe3O4 and platinum composite for the purpose of reusable and recyclable catalysis in Appendix 3. Emulsion as well as the electroless plating synthesis with poly(N-isopropylacrylamide) as the matrix were utilized.

参考文献 ( 237 ) 〈TOP〉

2. E. Gil and S. Hudson, Prog. Polym. Sci., 2004, 29, 1173-1222.
连结：
3. N. K. Singh and D. S. Lee, Journal of controlled release : official journal of the Controlled Release Society, 2014, 193, 214-227.
连结：
5. C. J. Lefaux, J. A. Zimberlin, A. V. Dobrynin and P. T. Mather, J. Polym. Sci., Part B: Polym. Phys., 2004, 42, 3654-3666.
连结：
7. N. Rapoport, Prog. Polym. Sci., 2007, 32, 962-990.
连结：
8. J. A. Hubbell, J. Controlled Release, 1996, 39, 305-313.
连结：

国际计量

〈TOP〉

E-mail ：

文章公开取用时，将寄通知信至您填写的信箱地址

E-mail ：

使用DOI作为永久连结

引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。