用于光动力治疗剂的氨基硅烷修饰的磁性纳米复合粒子载药体系的研究

发布时间：2018-05-17 12:19

  本文选题：纳米粒子 + 氨基硅烷　； 参考：《山西大学》2015年硕士论文

【摘要】：光动力疗法(PDT)是一种癌症治疗的新方法,其原理是受可见光照射的光敏剂分子吸收能量后,将能量传递给细胞中的氧分子,产生单线态氧或其它活性氧物种,从而导致细胞凋亡或坏死。目前用于PDT疗法的光敏剂多为脂溶性化合物,其水溶性较差,生物利用率较低且对正常细胞存在一定的细胞毒性。为此,本文系统地研究了氨基硅烷修饰的磁性纳米复合粒子作为光动力治疗剂的载药体系,以期在保留光动力治疗剂脂溶性的同时改善其水溶性。开展了以下工作：(1)合成了Fe3O4@SiO2纳米粒子,并采用两种氨基硅烷对其进行表面修饰,得到了具有一定的分散性和生物相容性的纳米复合粒子：Fe3O4@SiO2-APTES和Fe3O4@SiO2-AEAPS。采用IR、XRD等检测手段对所得的复合粒子进行结构表征,并测定了其Zeta电位。Fe3O4@SiO2-APTES和Fe3O4@SiO2-AEAPS两种纳米复合粒子的粒径分别为11.94 nm和12.85 nm,相应的Zeta电位分别为31.7 mV和32.7 mV。(2)将两种铂二亚胺类配合物,配合物Ⅰ和配合物Ⅱ负载到纳米复合粒子表面,得到了载药纳米粒子,通过紫外-可见吸光度法分别测定了纳米复合粒子的载药率。结果表明：Fe3O4@SiO2-APTES、Fe3O4@SiO2-AEAPS和(Fe3O4/TA)@SiO2对配合物Ⅰ的载药率分别为：7.6%,7.4%,7.5%；对配合物Ⅱ的载药率分别为8.4%,8.3%,8.5%。(3)通过琼脂糖凝胶电泳技术研究了载药纳米粒子对DNA的损伤行为。研究发现,表面带正电荷的纳米复合粒子Fe3O4@SiO2-APTES和Fe3O4@SiO2-AEAPS对DNA基本无损伤,而表面带负电荷的纳米复合粒子(Fe3O4/TA)@SiO2对DNA存在一定程度的损伤。上述三种纳米复合粒子载药后在光照条件下对DNA均存在一定损伤,且这种损伤程度与药物浓度呈正相关。(4)通过MTT实验探究了配合物以及载药纳米粒子对肿瘤细胞的细胞活性的影响。结果表明,光照条件下,配合物以及载药纳米粒子对细胞增殖均存在一定程度的抑制作用,且不同配合物对不同种类的肿瘤细胞的增殖抑制程度不同。就载药纳米粒子对细胞增殖的抑制程度而言,表面带正电荷的纳米复合粒子载药后对细胞增殖的抑制程度明显优于表面带负电荷的纳米复合粒子。(5)以流式细胞术测定了配合物及部分载药纳米粒子对MCF-7细胞周期的影响。结果表明,配合物及载药纳米粒子均对细胞周期不同阶段产生一定的阻滞作用,进而影响细胞的增殖。
[Abstract]:Photodynamic therapy (PDT) is a new method of cancer treatment. The principle is that molecules of Guang Min, irradiated by visible light, absorb energy and transfer it to oxygen molecules in cells to produce singlet oxygen or other reactive oxygen species. This leads to apoptosis or necrosis. At present, most of the Guang Min agents used in PDT therapy are liposoluble compounds, which have poor water solubility, low bioavailability and cytotoxicity to normal cells. In order to improve the water-solubility of the photodynamic therapy agent, the magnetic nanoparticles modified with aminosilane were studied systematically as the drug delivery system of the photodynamic therapy agent in order to preserve the liposolubility of the photodynamic therapy agent at the same time. Fe3O4@SiO2 nanoparticles were synthesized and modified by two kinds of aminosilane. The nano-composite particles: Fe3O4SiO2-APTES and Fe3O4SiO2-AEAPSs with certain dispersity and biocompatibility were obtained. The structure of the composite particles was characterized by IR XRD. The Zeta potential, Fe _ 3O _ 4r Sio _ 2-APTES and Fe3O4@SiO2-AEAPS nanoparticles were determined to be 11.94 nm and 12.85 nm, respectively, and the corresponding Zeta potentials were 31.7 MV and 32.7 mV.-2 respectively. The two kinds of platinum diimide complexes, complexes 鈪，

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