本文選題：環(huán)糊精　切入點：超分子　出處：《昆明理工大學》2017年碩士論文

【摘要】：超分子化學是由多種學科,例如化學、藥學、材料學、醫(yī)學等熱點研究領域,交叉而形成的一門新學科。超分子化學的自組裝一直是該領域中的熱門,很多具有新型結構和多重功能的有序可控的超分子組裝體都是利用了分子自組裝構筑出的。這種超分子組裝體的出現(xiàn)對于研究開發(fā)新型功能的基因/藥物遞送載體具有重大的研究意義。時至今日在超分子領域的探索中,環(huán)糊精已經成為了研究熱點之一,研究的最為廣泛是其中的分子識別、分子的自組裝和自組裝體功能化的應用。環(huán)糊精可以通過分子間的自組裝開發(fā)出大小可控,形貌可控的超分子載體。利用環(huán)糊精的自組裝還可以在分子水平上將具有多種功能的生物材料結合在一起,開發(fā)出一種多功能化的藥物或基因載體。與通過共價鍵合成的載體相比,通過環(huán)糊精自組裝構筑的功能化載體具有很大的優(yōu)勢,譬如,實驗所需反應條件平和,綠色環(huán)保,過程易控,功能化方便。本論文意在設計出基于環(huán)糊精自組裝構建的安全高效的藥物和基因載體。1.首先我們采用懸浮法制備了四種胺基環(huán)糊精,即單-6-氨基-β-環(huán)糊精(1N-β-CD),單-6-乙二胺-β-環(huán)糊精(2N-β-CD),單-6-二乙烯三胺-β-環(huán)糊精(3N-β-CD)和單-6-三乙烯四胺-β-環(huán)糊精(4N-β-CD)。隨后采用多種方法手段對大黃酸與四種胺基環(huán)糊精包合物的液相/固相性質進行了表征。最后,利用MTT法對包合物進行了體外抗癌活性的研究。結果表明,大黃酸與四種胺基環(huán)糊精形成了 1:1的主客體包合物,另外值得注意的是,四種胺基環(huán)糊精對大黃酸的水溶性及抗癌活性有了明顯的提高。2.基于環(huán)糊精超分子系統(tǒng)構筑出的非病毒性基因載體,在這項研究中,首先制備出丁二酸修飾的ε-聚賴氨酸枝接聚乙烯亞胺環(huán)糊精(PPC)以及金剛烷化的聚乙二醇(PEG-AD),并使PEG-AD與PPC進行自組裝形成復合物(PPPC)。我們對PPPC和PPC做了凝膠電泳阻滯實驗,顆粒粒徑,表面電荷等一系列生物物理特性的研究;然后用MTT法對PPPC和PPC的細胞毒性做了評估,最后對PPPC和PPC的轉染效率做了研究。結果表明,具有高穩(wěn)定性低毒的的復合物很可能成為一種遞送核酸的載體。
[Abstract]:Supramolecular chemistry is a new subject which is formed by the intersection of a variety of subjects, such as chemistry, pharmacy, materials, medicine, etc. The self-assembly of supramolecular chemistry has always been a hot topic in this field. Many ordered and controllable supramolecular assemblies with new structures and multiple functions are constructed from molecular self-assembly. The emergence of this supramolecular assembly is useful for the development of novel functional gene / drug delivery carriers. In the field of supramolecular exploration, Cyclodextrin has become one of the research hotspots, and the most widely studied is its molecular recognition, self-assembly and self-assembly functionalization. Cyclodextrin can be controlled by self-assembly between molecules. The self-assembly of cyclodextrin can also combine multi-functional biomaterials at the molecular level. A multifunctional drug or gene vector was developed. Compared with the vector synthesized by covalent bond, the functional vector constructed by self-assembly of cyclodextrin has great advantages, for example, the reaction conditions required for the experiment are mild and green. The purpose of this paper is to design a safe and efficient drug and gene vector based on cyclodextrin self-assembly. Firstly, four kinds of amino-cyclodextrin were prepared by suspension method. That is, single -6-amino-beta-cyclodextrin 1N- 尾 -CDA, mono-6-ethylenediamide- 尾 -cyclodextrin 2N- 尾 -CDA, mono-6-diethylenetriethyltriamine- 尾 -cyclodextrin 3N- 尾 -CD) and mono-6-triethylenetetramethylamin- 尾 -cyclodextrin 4N- 尾 -CD-CD.Then, various methods were used to study the inclusion of Rheoic acid with four kinds of amine cyclodextrins. The liquid / solid phase properties were characterized. Finally, The in vitro anticancer activity of the inclusion complex was studied by MTT method. The results showed that Rhein and four kinds of amino cyclodextrin formed a 1:1 inclusion compound with host and guest. The water-solubility and anticancer activity of four kinds of amino cyclodextrins against Rhein have been significantly improved .2. based on the non-viral gene vector constructed by cyclodextrin supramolecular system, in this study, First, the modified 蔚 -poly (lysine) imine cyclodextrin (PPC) and the adamantanized polyethylene glycol (PEG-ADN) were prepared, and PEG-AD and PPC were self-assembled to form the complex. We performed gel electrophoresis arrest experiments on PPPC and PPC, and the particle size was determined. A series of biophysical properties such as surface charge were studied, then the cytotoxicity of PPPC and PPC was evaluated by MTT method, and the transfection efficiency of PPPC and PPC was studied. Complex with high stability and low toxicity is likely to be a carrier for delivery of nucleic acid.
【學位授予單位】：昆明理工大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：O641.3;TQ460.1

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相關期刊論文 前2條

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本文編號：1655982