基于环糊精自组装构筑的药物和基因载体的研究

发布时间：2018-03-24 01:02

本文选题：环糊精　切入点：超分子　出处：《昆明理工大学》2017年硕士论文

【摘要】：超分子化学是由多种学科,例如化学、药学、材料学、医学等热点研究领域,交叉而形成的一门新学科。超分子化学的自组装一直是该领域中的热门,很多具有新型结构和多重功能的有序可控的超分子组装体都是利用了分子自组装构筑出的。这种超分子组装体的出现对于研究开发新型功能的基因/药物递送载体具有重大的研究意义。时至今日在超分子领域的探索中,环糊精已经成为了研究热点之一,研究的最为广泛是其中的分子识别、分子的自组装和自组装体功能化的应用。环糊精可以通过分子间的自组装开发出大小可控,形貌可控的超分子载体。利用环糊精的自组装还可以在分子水平上将具有多种功能的生物材料结合在一起,开发出一种多功能化的药物或基因载体。与通过共价键合成的载体相比,通过环糊精自组装构筑的功能化载体具有很大的优势,譬如,实验所需反应条件平和,绿色环保,过程易控,功能化方便。本论文意在设计出基于环糊精自组装构建的安全高效的药物和基因载体。1.首先我们采用悬浮法制备了四种胺基环糊精,即单-6-氨基-β-环糊精(1N-β-CD),单-6-乙二胺-β-环糊精(2N-β-CD),单-6-二乙烯三胺-β-环糊精(3N-β-CD)和单-6-三乙烯四胺-β-环糊精(4N-β-CD)。随后采用多种方法手段对大黄酸与四种胺基环糊精包合物的液相/固相性质进行了表征。最后,利用MTT法对包合物进行了体外抗癌活性的研究。结果表明,大黄酸与四种胺基环糊精形成了 1:1的主客体包合物,另外值得注意的是,四种胺基环糊精对大黄酸的水溶性及抗癌活性有了明显的提高。2.基于环糊精超分子系统构筑出的非病毒性基因载体,在这项研究中,首先制备出丁二酸修饰的ε-聚赖氨酸枝接聚乙烯亚胺环糊精(PPC)以及金刚烷化的聚乙二醇(PEG-AD),并使PEG-AD与PPC进行自组装形成复合物(PPPC)。我们对PPPC和PPC做了凝胶电泳阻滞实验,颗粒粒径,表面电荷等一系列生物物理特性的研究;然后用MTT法对PPPC和PPC的细胞毒性做了评估,最后对PPPC和PPC的转染效率做了研究。结果表明,具有高稳定性低毒的的复合物很可能成为一种递送核酸的载体。
[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.
【学位授予单位】：昆明理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O641.3;TQ460.1

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