本文選題：光動力療法 + 金屬鉑配合物�。� 參考：《山西大學(xué)》2017年碩士論文

【摘要】：癌癥日益威脅著人類的生命健康,但迄今為止并沒有非常安全有效的癌癥治療方法,傳統(tǒng)的治療癌癥方法還存在著很多缺點,科學(xué)工作者正在不斷地研究更有效安全的癌癥治療方法。上世紀末,光動力療法(photodynamic therapy,PDT)被用于癌癥治療。它表現(xiàn)出特有的優(yōu)點,如對腫瘤組織有選擇性,藥物毒副作用小,與傳統(tǒng)手術(shù)療法結(jié)合后可降低術(shù)后復(fù)發(fā)率等,因此光動力療法成為了治療癌癥的一種新的選擇。光動力反應(yīng)是指光敏物質(zhì)經(jīng)光照作用后產(chǎn)生活性氧導(dǎo)致細胞損傷和壞死的作用,此反應(yīng)在生物學(xué)和醫(yī)學(xué)中被用于疾病的診斷和治療,即光動力療法。光動力療法的治療效果主要取決于光敏劑經(jīng)光照后產(chǎn)生可損傷細胞的活性物質(zhì)單線態(tài)氧的能力。鉑二亞胺類配合物是一類過渡金屬配合物,其分子結(jié)構(gòu)呈平面型,配合物MLCT/LLC T躍遷的最大吸收波長處于近紅外光區(qū)。研究表明該類配合物避光條件下理化性質(zhì)穩(wěn)定,光照后可產(chǎn)生大量的單線態(tài)氧,可作為光動力療法的光敏劑。對此類光敏劑的配體進行結(jié)構(gòu)修飾,有望進一步提高其光動力活性,使其最大吸收波長紅移。同時以表面改性后的磁性納米復(fù)合粒子作為光敏藥物的載體,可改善光敏劑的靶向性和生物相容性。本文通過大量文獻調(diào)研,合成表征了一種新型鉑二亞胺類配合物,檢測了它產(chǎn)生單線態(tài)氧的能力,再將配合物負載至生物相容性較好的兩種磁性納米復(fù)合粒子后,研究了此類配合物及載藥磁性納米粒子與DNA的作用效果,進一步研究了配合物對肝癌細胞SMMC-7721的作用效果。具體工作如下:一、合成一種新的鉑二亞類配合物Pt(4-Br-OPDI)_2,同時根據(jù)文獻合成配合物Pt(DIBA-Na)(OPDI),以紫外-可見吸收光譜、元素分析等方法表征配合物的結(jié)構(gòu)。二、采用化學(xué)捕獲法,以DPBF為化學(xué)捕獲劑,比較了配合物Pt(4-Br-OPDI)_2、Pt(DIBA-Na)(OPDI)和Pt(4-Br-OPDI)(OPDI)經(jīng)紅光光照后產(chǎn)生單線態(tài)氧的能力。結(jié)果表明,Pt(4-Br-OPDI)_2產(chǎn)生單線態(tài)氧的能力強于其他二者,光動力活性較高。三、通過物理吸附的方法分別將配合物Pt(4-Br-OPDI)_2和Pt(DIBA-Na)(OPDI)負載于表面改性后的磁性納米粒子(Fe_3O_4/TA)@Si O_2和Fe_3O_4@Si O_2-APTES上,采用紫外-可見吸收光譜法和標準曲線測定載藥納米粒子的載藥率。結(jié)果表明,磁性納米粒子(Fe_3O_4/TA)@Si O_2和Fe_3O_4@Si O_2-APTES負載配合物Pt(4-Br-OPDI)_2后的載藥率分別為6.8%和4.5%,負載配合物Pt(DIBA-Na)(OPDI)后的載藥率分別為7.6%和5.3%。四、以瓊脂糖凝膠電泳法研究了配合物和載藥納米粒子與p BR322 DNA的相互作用。研究表明,配合物經(jīng)紅光光照后對DNA有明顯損傷作用,載藥納米粒子光照后對DNA損傷作用增強,未經(jīng)光照,配合物和載藥納米粒子對DNA損傷作用較弱甚至無損傷。五、采用MTT比色法研究了兩種配合物對SMMC-7721細胞增殖的抑制作用。其中配合物Pt(4-Br-OPDI)_2在有無光照條件下均對癌細胞增殖有一定程度的抑制作用,光照組表現(xiàn)出光動力活性對細胞中增殖的抑制作用。配合物Pt(DIBA-Na)(OPDI)在有無光照的條件下均未對SMMC-7721細胞的增殖表現(xiàn)出抑制效果,說明該配合物對此類癌細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.
【學(xué)位授予單位】：山西大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R730.5;O641.4

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