含PEG链段超支化聚合物的合成、修饰及其与纳米材料的复合组装

发布时间：2018-11-11 13:38

【摘要】：近年来,超支化聚合物因具有多个侧链结构,以及侧链末端引入的多种多样可拓展修饰的官能团而引起了广泛关注,其中最常见的两类为带有多个侧链的刷型共聚物和超支化树枝状大分子。本文通过原子转移自由基聚合反应制得含PEG侧链的两嵌段共聚物,经过功能化修饰接入不同的官能团,成为一个即插即用的灵活通用的多功能反应平台,可用来与磁性纳米颗粒进行自组装形成多功能纳米复合材料。此外,将树枝状大分子和疏水性的小分子同时与氧化石墨烯反应,以获得双亲性的新型药物载体,可用于抗炎治疗等生物医学领域。主要工作如下:1.在本项工作中,通过原子转移自由基聚合(ATRP)的方法制得含PEG侧链的刷型嵌段共聚物,并进一步验证其作为即插即用多功能性单元的可行性。刷型嵌段共聚物主要包括三部分:(i)亲水性的PEGMA侧链;(ii)PEGMEMA侧链,其末端的羟基可以通过酯化反应和叠氮化反应转变为-N3基团;(iii)末端带有羧基的PMAA侧链,其中羧基是通过叔丁基的水解羧酸化制备得到的。这三种侧链均具有相应的功能,其中,PEG侧链因其良好的亲水性和生物相容性,可使所制复合材料拥有良好的稳定性,叠氮基团可用于和末端炔基的分子进行点击化学反应;羧基由于带负电荷,可与带正电的离子或者分子通过静电吸引的方式组装形成新型的多功能纳米复合材料。所制聚合物的结构通过核磁共振氢谱(1HNMR)和凝胶渗透色谱(GPC)分别进行表征,通过动态激光散射、Zeta电位和荧光光谱等方法研究了聚合物胶束和纳米颗粒的自组装行为,另外,将聚合物与多巴胺修饰的四氧化三铁纳米颗粒通过静电复合形成稳定的多功能磁性纳米颗粒。本项工作提供了一种新的方法用于制备多功能的双亲性聚合物和磁性纳米材料。2.本项工作中,通过对氧化石墨烯表面羧基的选择性保护和脱保护,分别将疏水小分子十八烷基异氰酸酯(ODI)和亲水性良好的树枝状大分子(Dendrimer)顺序接枝到氧化石墨烯材料表面,制得内部疏水外部亲水的新型双亲性氧化石墨烯材料(Dendrimer-GO-ODI),并通过π-π堆叠作用将疏水药物姜黄素负载到石墨烯表面,制得基于改性氧化石墨烯材料的药物载体。研究了负载姜黄素的改性氧化石墨烯材料的药物释放规律,以及对BV2神经小胶质细胞的炎症治疗效果。与氧化石墨烯相比,改性氧化石墨烯材料的载药率远远高于未经改性的氧化石墨烯,而且,改性氧化石墨烯材料负载的姜黄素可实现逐渐缓慢释放,与纯药对照组相比,具有更好的抗炎治疗效果,证明所制新型双亲性氧化石墨烯材料在药物载体领域具有广阔的应用前景。
[Abstract]:In recent years, hyperbranched polymers have attracted wide attention due to their multiple side chain structures and various extensible modified functional groups introduced at the end of side chains. The two most common types are brush copolymers with multiple side chains and hyperbranched macromolecules. In this paper, two block copolymers containing side chains of PEG were prepared by atom transfer radical polymerization. The copolymers were functionalized and connected to different functional groups, which became a flexible and universal multifunctional reaction platform for plug and play. It can be used to self-assemble magnetic nanoparticles to form multi-functional nanocomposites. In addition, dendritic macromolecules and hydrophobic small molecules reacted with graphene oxide at the same time to obtain novel amphiphilic drug carriers, which can be used in anti-inflammatory therapy and other biomedical fields. The main work is as follows: 1. In this work, the brush-type block copolymers containing side chains of PEG were prepared by atom transfer radical polymerization of (ATRP), and the feasibility of using them as plug and play multifunctional units was further verified. The brush-type block copolymers mainly consist of PEGMA side chains with three parts of: (i) hydrophilic; (ii) PEGMEMA. The hydroxyl groups at the end of the copolymers can be transformed into -N3 groups by esterification and azide reactions. The side chain of PMAA with carboxyl group at the end of (iii) was prepared by hydrolyzing carboxylation of tertiary Ding Ji. The PEG side chain has good stability because of its good hydrophilicity and biocompatibility. The azide group can be used for click-reaction with the terminal alkynyl molecule. Carboxyl groups with negative charge can be assembled with positively charged ions or molecules by electrostatic attraction to form a new type of multifunctional nanocomposites. The structure of the polymer was characterized by nuclear magnetic resonance (1HNMR) and gel permeation chromatography (GPC) respectively. The self-assembly behavior of polymer micelles and nanoparticles was studied by means of dynamic laser scattering, Zeta potential and fluorescence spectroscopy. In addition, the polymer and dopamine modified Fe _ 2O _ 3 nanoparticles were prepared by electrostatic recombination to form stable multifunctional magnetic nanoparticles. This work provides a new method for the preparation of multifunctional amphiphilic polymers and magnetic nanomaterials. In this work, selective protection and deprotection of the carboxyl groups on the surface of graphene oxide, The hydrophobic small molecule octadecyl isocyanate (ODI) and the hydrophilic dendritic macromolecule (Dendrimer) were grafted to the surface of graphene oxide, respectively. A novel amphiphilic graphene oxide material (Dendrimer-GO-ODI) with internal hydrophobic and external hydrophilicity was prepared, and the hydrophobic drug curcumin was loaded onto the surface of graphene by 蟺-蟺 stacking to prepare the drug carrier based on the modified graphene oxide material. The drug release rule of modified graphene oxide loaded with curcumin and its effect on inflammation of BV2 neural microglia were studied. Compared with graphene oxide, the drug loading rate of the modified graphene oxide material is much higher than that of the unmodified graphene oxide material. Moreover, curcumin loaded with the modified graphene oxide material can be released slowly, compared with the control group. It is proved that the new amphiphilic graphene oxide material has a broad application prospect in the field of drug carrier.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：O631;TB33

【相似文献】