不同基团修饰的铂二亚胺类配合物的光动力活性研究

发布时间：2018-05-23 21:10

本文选题：光动力疗法 + 金属铂配合物　；参考：《山西大学》2017年硕士论文

【摘要】：癌症日益威胁着人类的生命健康,但迄今为止并没有非常安全有效的癌症治疗方法,传统的治疗癌症方法还存在着很多缺点,科学工作者正在不断地研究更有效安全的癌症治疗方法。上世纪末,光动力疗法(photodynamic therapy,PDT)被用于癌症治疗。它表现出特有的优点,如对肿瘤组织有选择性,药物毒副作用小,与传统手术疗法结合后可降低术后复发率等,因此光动力疗法成为了治疗癌症的一种新的选择。光动力反应是指光敏物质经光照作用后产生活性氧导致细胞损伤和坏死的作用,此反应在生物学和医学中被用于疾病的诊断和治疗,即光动力疗法。光动力疗法的治疗效果主要取决于光敏剂经光照后产生可损伤细胞的活性物质单线态氧的能力。铂二亚胺类配合物是一类过渡金属配合物,其分子结构呈平面型,配合物MLCT/LLC T跃迁的最大吸收波长处于近红外光区。研究表明该类配合物避光条件下理化性质稳定,光照后可产生大量的单线态氧,可作为光动力疗法的光敏剂。对此类光敏剂的配体进行结构修饰,有望进一步提高其光动力活性,使其最大吸收波长红移。同时以表面改性后的磁性纳米复合粒子作为光敏药物的载体,可改善光敏剂的靶向性和生物相容性。本文通过大量文献调研,合成表征了一种新型铂二亚胺类配合物,检测了它产生单线态氧的能力,再将配合物负载至生物相容性较好的两种磁性纳米复合粒子后,研究了此类配合物及载药磁性纳米粒子与DNA的作用效果,进一步研究了配合物对肝癌细胞SMMC-7721的作用效果。具体工作如下:一、合成一种新的铂二亚类配合物Pt(4-Br-OPDI)_2,同时根据文献合成配合物Pt(DIBA-Na)(OPDI),以紫外-可见吸收光谱、元素分析等方法表征配合物的结构。二、采用化学捕获法,以DPBF为化学捕获剂,比较了配合物Pt(4-Br-OPDI)_2、Pt(DIBA-Na)(OPDI)和Pt(4-Br-OPDI)(OPDI)经红光光照后产生单线态氧的能力。结果表明,Pt(4-Br-OPDI)_2产生单线态氧的能力强于其他二者,光动力活性较高。三、通过物理吸附的方法分别将配合物Pt(4-Br-OPDI)_2和Pt(DIBA-Na)(OPDI)负载于表面改性后的磁性纳米粒子(Fe_3O_4/TA)@Si O_2和Fe_3O_4@Si O_2-APTES上,采用紫外-可见吸收光谱法和标准曲线测定载药纳米粒子的载药率。结果表明,磁性纳米粒子(Fe_3O_4/TA)@Si O_2和Fe_3O_4@Si O_2-APTES负载配合物Pt(4-Br-OPDI)_2后的载药率分别为6.8%和4.5%,负载配合物Pt(DIBA-Na)(OPDI)后的载药率分别为7.6%和5.3%。四、以琼脂糖凝胶电泳法研究了配合物和载药纳米粒子与p BR322 DNA的相互作用。研究表明,配合物经红光光照后对DNA有明显损伤作用,载药纳米粒子光照后对DNA损伤作用增强,未经光照,配合物和载药纳米粒子对DNA损伤作用较弱甚至无损伤。五、采用MTT比色法研究了两种配合物对SMMC-7721细胞增殖的抑制作用。其中配合物Pt(4-Br-OPDI)_2在有无光照条件下均对癌细胞增殖有一定程度的抑制作用,光照组表现出光动力活性对细胞中增殖的抑制作用。配合物Pt(DIBA-Na)(OPDI)在有无光照的条件下均未对SMMC-7721细胞的增殖表现出抑制效果,说明该配合物对此类癌细胞增殖的抑制作用甚微。
[Abstract]:Cancer is increasingly threatening human life and health, but so far there are no very safe and effective methods of cancer treatment. There are many shortcomings in traditional cancer treatment methods. Scientists are constantly studying the more effective and safe methods of cancer treatment. At the end of the last century, photodynamic therapy (PDT) was used for cancer. It shows unique advantages, such as the selectivity to the tumor tissue, the small side effect of the drug, and the reduction of the recurrence rate after the combination of the traditional surgical treatment. Therefore, photodynamic therapy has become a new choice for the treatment of cancer. The effect of the reaction in biology and medicine used in the diagnosis and treatment of diseases, namely photodynamic therapy. The therapeutic effect of photodynamic therapy mainly depends on the ability of photosensitizers to produce the single state oxygen of active substances that can damage cells after illumination. The platinum two imine complex is a class of transition metal complexes and its molecular structure The maximum absorption wavelength of the complex MLCT/LLC T transition is in the near infrared light region. The study shows that the complexes are stable in physical and chemical properties under light avoiding conditions and can produce a large number of single state oxygen after illumination, which can be used as photosensitizers for photodynamic therapy. The modification of the ligand in this kind of photosensitizer is expected to further improve its photodynamic. In this paper, a new type of platinum two imide complex has been synthesized and characterized by a large number of literature investigation and investigation. After the compound was loaded with two kinds of magnetic nanocomposite particles with good biocompatibility, the effects of such complexes and drug loaded magnetic nanoparticles and DNA were studied, and the effects of the complexes on liver cancer cell SMMC-7721 were further studied. The specific work is as follows: 1, a new platinum two subclass complex, Pt (4-Br-OPDI) _2, is synthesized. According to the bibliographical complex Pt (DIBA-Na) (OPDI), the complex structure was characterized by UV visible absorption spectrum and elemental analysis. Two, the chemical capture method and DPBF as the chemical capture agent were used to compare the ability to produce the single state oxygen after the red light illumination of the complex Pt (4-Br-OPDI) _2, Pt (DIBA-Na) (OPDI) and Pt (4-Br-OPDI). The results show that the ability of Pt (4-Br-OPDI) _2 to produce single state oxygen is stronger than the other two, and the photodynamic activity is higher. Three, the magnetic nanoparticles (4-Br-OPDI) _2 and Pt (DIBA-Na) (OPDI) are loaded on the surface modified magnetic nanoparticles (Fe_3O_4/TA) @Si O_2 and on the surface by physical adsorption. The UV visible absorption spectrum method is used. The drug loading rate of drug loaded nanoparticles was measured with the standard curve. The results showed that the drug loading rates of the magnetic nanoparticles (Fe_3O_4/TA) @Si O_2 and Fe_3O_4@Si O_2-APTES loaded complex Pt (4-Br-OPDI) _2 were 6.8% and 4.5% respectively. The loading rates of the loaded complexes Pt (DIBA-Na) (OPDI) were 7.6% and 5.3%. four respectively, and the agarose gel electrophoresis was used to study the drug loading rate respectively. The interaction of complexes and drug loaded nanoparticles with P BR322 DNA. The study shows that the complexes have obvious damage to DNA after red light illumination. The effect of drug loaded nanoparticles on DNA damage is enhanced after light irradiation. The effects of the complexes and drug loaded nanoparticles on DNA damage are weak and even without damage. Five, the MTT colorimetric method is used to study two. The inhibitory effect of the complexes on the proliferation of SMMC-7721 cells, in which the complex Pt (4-Br-OPDI) _2 has a certain degree of inhibition on the proliferation of cancer cells under light conditions, and the light group shows the inhibitory effect of photodynamic activity on the proliferation of cells. The complex Pt (DIBA-Na) (OPDI) is not fine to SMMC-7721 under the conditions of light. Cell proliferation showed inhibitory effect, indicating that the complex had little inhibitory effect on the proliferation of such cancer cells.
【学位授予单位】：山西大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R730.5;O641.4

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