包含碱基对的智能型超分子水凝胶的合成及应用

发布时间：2018-05-04 06:31

本文选题：水凝胶 + 氢键　；参考：《东北师范大学》2017年硕士论文

【摘要】：1953年,James Watson和Francis Crick提出了DNA的双螺旋结构,发现互补的碱基对A-T(adenine thymine)和G-C(guanine cytosine)之间以氢键作为桥梁,构筑起了DNA双螺旋结构。由于多重碱基对在组装方面有着高度的精确性和方向性,碱基对的概念就由生物领域跨越到超分子化学领域。虽然碱基对在超分子领域已经发挥了重要的作用,但是其在生物医用高分子领域的应用还只是处于刚刚起步的阶段。另一方面,传统的PEG/α-CD超分子水凝胶的力学性能并不是十分理想,还有很大的提高空间。本论文以具有良好生物相容性的聚乙二醇为骨架,在传统的PEG/α-CD水凝胶的基础上引入C-G碱基对,构建了包含碱基对的刺激响应性的水凝胶。C-G碱基对的引入,明显地增加了交联点的数量,增加了交联密度,形成的凝胶具有更强的力学性能。在增加交联密度,提高力学性能的前提下,通过引入刺激响应性的官能团构建了智能性的超分子水凝胶,本论文主要包括以下两方面内容:1.在PEG/α-CD超分子水凝胶的构建过程中,引入胞嘧啶(C)/鸟嘌呤(G)碱基对,制备温度敏感的超分子凝胶。实验证明表明:C-G间碱基对的引入,提高了PEG/α-CD超分子凝胶体系的交联密度,超分子凝胶的力学性能明显提高。进一步,以阿霉素(DOX)为抗癌药物模型,探讨包含碱基对超分子水凝胶作为药物载体的可行性,体外药物释放数据表明:包含碱基对的PEG/α-CD超分子水凝胶(SHG)对DOX有很好的缓释效果。体外细胞毒性实验也证明,SHG超分子水凝胶具有良好的生物相容性,在生物医用材料方面具有优异的应用前景。2.在第一章研究内容的基础上,选用具有活性氧自由基敏感的酮缩硫醇键连接碱基对,用鸟嘌呤修饰的酮缩硫醇键(G-TK-G)将胞嘧啶修饰的PEG(C-PEG-C)连接起来,与α-CD一起,构建了含有TK键的ROS敏感的超分子水凝胶(TKHG)。评价了智能型超分子水凝胶的ROS敏感性,并研究了该类水凝胶对对抗肿瘤药物的担载及ROS响应性释放。结果表明:制备的TKHG具有增强的力学性能,并对DOX有很好的ROS响应性释放效果。
[Abstract]:In 1953, James Watson and Francis Crick proposed the double helix structure of DNA. It was found that the double helix structure of DNA was constructed by hydrogen bond between the complementary base pair A-T(adenine thymine) and G-C(guanine cytosine. Because of its high accuracy and directivity in the assembly of multiplex base pairs, the concept of base pairs leaps from the field of biology to the field of supramolecular chemistry. Although base pair has played an important role in the field of supramolecular, its application in biomedical polymer field is still in its infancy. On the other hand, the mechanical properties of traditional PEG/ 伪 -CD supramolecular hydrogels are not ideal, and there is much room for improvement. In this paper, based on polyethylene glycol with good biocompatibility, C-G base pair was introduced on the basis of traditional PEG/ 伪 -CD hydrogel, and a hydrogel. C-G base pair containing base pair was constructed. The number of crosslinking points and crosslinking density were obviously increased, and the resulting gel had stronger mechanical properties. On the premise of increasing crosslinking density and improving mechanical properties, intelligent supramolecular hydrogels were constructed by introducing stimulus-responsive functional groups. The main contents of this thesis are as follows: 1. In the process of constructing PEG/ 伪 -CD supramolecular hydrogel, the temperature sensitive supramolecular gel was prepared by introducing cytosine Con / guanine G base pair. The results show that the cross-linking density and mechanical properties of PEG/ 伪 -CD supermolecular gels are improved by the introduction of the 1: C-G base pair. Furthermore, the feasibility of supramolecular hydrogels containing base pairs as drug carriers was investigated by using doxorubicin (DOX) as an anticancer drug model. In vitro drug release data showed that PEG/ 伪 -CD supramolecular hydrogels containing base pairs had a good sustained release effect on DOX. In vitro cytotoxicity tests also proved that SHG supramolecular hydrogels have good biocompatibility and have excellent application prospects in biomedical materials. On the basis of the research in the first chapter, the keto-mercaptan bond, which is sensitive to reactive oxygen free radical, is selected to connect the base pair, and the guanine modified ketothiol bond (G-TK-G) is used to connect the cytosine modified PEGG C-PEG-C with 伪 -CD. A ROS sensitive supramolecular hydrogel with TK bond was constructed. The ROS sensitivity of intelligent supramolecular hydrogels was evaluated, and the loading and ROS responsive release of these hydrogels to anticancer drugs were studied. The results show that the prepared TKHG has enhanced mechanical properties and has a good ROS response release effect on DOX.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O648.17

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