超分子系统的构建以及聚集诱导发光高分子作为基因载体的性能研究

发布时间：2018-01-13 19:34

本文关键词：超分子系统的构建以及聚集诱导发光高分子作为基因载体的性能研究　出处：《天津理工大学》2017年硕士论文　论文类型：学位论文

【摘要】：超分子纳米粒子(SNPs)通过特殊的多种非共价的超分子之间的作用力组成。与传统的高分子相比,超分子高分子的链条是通过非共价力连接的,比如氢键、主客体作用力、静电力等,并且制备过程也比较简单。尽管在超分子纳米粒子中复杂的作用力方面有许多成果,然而,仍然没有足够的研究来解释静电力和主客体作用力在超分子纳米粒子的粒径大小和稳定性的控制作用。之前研究过的系统主要集中在单一的作用力或者静电力与主客体作用力的协同作用,而在本研究中,我们致力于构建斥力与引力的平衡系统,获得既稳定又生物相容性良好的复合体,有望代替耗时又繁琐的传统纳米粒子的制备步骤。我们应用环氧基开环反应合成了PGMA上修饰有4-叔丁基苯胺和乙二胺的、带有正电荷的聚合物P+TBP。4-叔丁基苯胺可以和?-环糊精(CD)通过主客体作用复合。P+TBP分别和带有正电荷的P+CD和中性的PCD还有带有负电荷的P-CD复合。P+TBP与P+CD之间通过主客体的吸引力和相同电荷的斥力达到一种平衡,从而在不借助外界阻断剂或者化学键的方式下形成稳定的纳米粒子。结合成像与治疗的纳米粒子有利于同时进行影像诊断和治疗,在癌症的诊疗领域有着巨大的需求。在现今各种诊疗平台中,光动力疗法(PDT)是一种很有前景的方法,其具有很多优势,比如精确可控性,微创性和高时空精确性等。PDT的作用机制是:光敏剂在光照射下产生有毒的活性氧(ROS),可以抑制甚至破坏肿瘤细胞。本研究合成在近红外(NIR)具有聚集诱导发光(AIE)效应的阳离子小分子,用来示踪高分子/DNA复合体在细胞内的分布,避免光漂白作用和聚集荧光淬灭。AIE小分子修饰的阳离子高分子与质粒DNA通过正负电荷发生复合,用来示踪其在细胞内和体内的分布。AIE荧光团还可以产生活性氧(ROS)。将AIE引入细胞毒性较低的二硫键交联的寡聚乙烯亚胺阳离子高分子中,使用色氨酸对高分子进行修饰,提高其与DNA和细胞膜的结合能力,从而提高转染效率。
[Abstract]:Supramolecular nanoparticles (SNPs) are composed of special non-covalent supramolecular forces. Compared with conventional polymers, the chains of supramolecular polymers are connected by non-covalent forces. For example, hydrogen bonds, host-guest forces, electrostatic forces, and so on, and the preparation process is relatively simple, although there are many achievements in the complex forces in supramolecular nanoparticles, however. There is still not enough research to explain the control of hydrostatic power and host-guest forces on the particle size and stability of supramolecular nanoparticles. The synergy of the force between the subject and the object. In this study, we focus on constructing a repulsive and gravitational equilibrium system to obtain a stable and biocompatible complex. We used epoxide ring opening reaction to synthesize 4- tert-#china_person0# aniline and ethylenediamine modified on PGMA. A positively charged polymer, P-TBP.4- tert-#china_person0# aniline, can be associated with? -cyclodextrin (CD). P TBP and positive charge PCD and neutral PCD and negative charge P-CD compound. P TBP and P. A balance is achieved between the CD by the attraction of the host and the guest and the repulsive force of the same charge. In order to form stable nanoparticles without the help of external blockers or chemical bonds. The combination of imaging and treatment of nanoparticles is conducive to imaging diagnosis and treatment at the same time. In the field of diagnosis and treatment of cancer, there is a huge demand. Photodynamic therapy (PDT) is a promising method in all kinds of diagnostic and treatment platforms. It has many advantages, such as precision controllability. The mechanism of PDT, such as minimally invasive and high spatio-temporal accuracy, is that Guang Min produces toxic reactive oxygen species (Ros) under light irradiation. In this study, we synthesized cationic small molecules with aggregation induced luminescence (AIEs) effect at near infrared (NIR). It can be used to trace the distribution of polymer / DNA complex in cells to avoid the combination of photobleaching and fluorescence quenching. AIE modified cationic polymer and plasmid DNA by positive and negative charge. AIE fluorescent group can also produce reactive oxygen species (Ros). AIE was introduced into oligopolyethyleneimide cationic polymer with low cytotoxicity and disulfide bond crosslinking. Tryptophan was used to modify the polymer to improve its binding ability to DNA and cell membrane, thus enhancing the transfection efficiency.
【学位授予单位】：天津理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943

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