不同表面修饰的金纳米棒的小鼠体内代谢研究

发布时间：2018-06-05 04:00

本文选题：金纳米棒 + 表面修饰　；参考：《华南农业大学》2016年硕士论文

【摘要】：在纳米科技快速发展的今天,越来越多的人工纳米材料应用到社会的各个领域中。凭借其独特的理化性质,纳米材料广泛应用于电子、轮胎、燃料电池和体外诊断、局部成像、药物输送和体内治疗。在这些材料中,金纳米材料具有明显的表面效应,量子效应,小尺寸效应和生物相容性,成为光电子、催化和生物医药等领域的研究和应用的热点。目前,除金纳米球之外,金纳米棒正在被广泛研究,已成为生物传感器、癌细胞成像、分子检测、医疗诊断、药物运输和生物探针等生物医学领域中最具有前途的材料。然而,金纳米棒在体内的吸收、分布和积累等生物效应与其长径比、表面电荷、形状、表面积等因素密切相关。当金纳米棒接触到细胞或蛋白时,纳米颗粒表面和蛋白会发生物理化学作用,形成一个生物-纳米界面,从而引起金纳米棒(AuNRs)理化性质的改变。因此,当纳米材料通过静脉注射进入到血液中,血液中复杂的蛋白复合物会竞相形成蛋白层。纳米颗粒能够被血液中高浓度和高结合率的蛋白包覆而形成“蛋白冠”。蛋白冠的形成能够改变金纳米棒的大小和表面组成,从而影响材料的吸收、运输和毒性。为了更加准确了解金纳米棒在体内的代谢和毒性,本研究选取了四种不同表面修饰的长径比为3.8的金纳米棒,包括CTAB-AuNR,MS-AuNR,IMS-AuNR和MSA-AuNR,以CD-1品种的小鼠为模型,通过一次性尾静脉注射的暴露方式对小鼠进行染毒,选取1,3,7,28天等几个不同的时间点,观察了小鼠体内肝脏、脾脏和肾脏组织形态以及谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBil)、总蛋白(TP)、白蛋白(ALB)、球蛋白(GLOB)、葡萄糖(GLU)、谷胺酰转肽酶(GGT)、碱性磷酸酶(ALP)总胆汁酸(TBA)等生化指标的变化,探讨了金纳米棒在体内的吸收、分布、转运和毒性机制。结果显示:大约70%的AuNRs位于小鼠肝脏中,肝脏和脾脏是金纳米颗粒分布和代谢的两个重要器官;富集的AuNRs会对肝脏产生损伤,其中CTAB-AuNR组小鼠的肝脏损伤更严重,其毒性主要来源于CTAB,而有“蛋白冠”形成的纳米材料具有良好的生物相容性;进入肝脏的AuNRs位于肝枯否细胞的溶酶体中,导致小鼠机体在前期出现脂质过氧化,依靠体内的抗氧化防御系统使其恢复正常。
[Abstract]:With the rapid development of nanotechnology, more and more artificial nanomaterials are applied in various fields of society. With their unique physical and chemical properties, nanomaterials are widely used in electronics, tires, fuel cells and in vitro diagnostics, local imaging, drug delivery and in vivo therapy. Among these materials, gold nanomaterials have obvious surface effects, quantum effects, small size effects and biocompatibility, which have become the focus of research and application in photoelectron, catalysis and biomedicine. At present, besides gold nanospheres, gold nanorods have been widely studied and become the most promising biomedical materials in biosensors, cancer cell imaging, molecular detection, medical diagnosis, drug transportation and biomedical probes. However, the absorption, distribution and accumulation of gold nanorods in vivo are closely related to the aspect ratio, surface charge, shape and surface area of gold nanorods. When gold nanorods come into contact with cells or proteins, the surface of nanoparticles and proteins will take place physical and chemical interaction, forming a biological nanoscale interface, which will cause the change of physical and chemical properties of au nanorods (AuNRs). Therefore, when nanomaterials are injected intravenously into the blood, complex protein complexes in the blood compete to form a protein layer. Nanoparticles can be coated with high concentrations and high binding rates of proteins in the blood to form a protein crown. The formation of protein crown can change the size and surface composition of gold nanorods, thus affecting the absorption, transport and toxicity of materials. In order to understand more accurately the metabolism and toxicity of gold nanorods in vivo, four kinds of gold nanorods with different aspect ratio of length to diameter of 3.8 were selected, including CTAB-AuNRU MS-AuNRCIMS-AuNR and MSA-AuNR. The mice were exposed to one dose of caudal vein injection for 28 days, and the liver of the mice was observed. The changes of spleen and kidney histomorphology, alanine aminotransferase (alt), alanine aminotransferase (AST), total bilirubin (TBiln), total protein (TPN), Albumin (ALB), globulin (GLOBN), glucose (GLU), glutamyl transpeptidase (GGTT), alkaline phosphatase (ALP), total bile acid (TBA), and so on. The mechanism of absorption, distribution, transport and toxicity of gold nanorods in vivo was discussed. The results showed that about 70% of AuNRs was located in the liver of mice. Liver and spleen were two important organs of distribution and metabolism of gold nanoparticles, and the liver was damaged by enriched AuNRs, especially in CTAB-AuNR group. Its toxicity is mainly derived from CTAB, and the nano-materials formed by "protein crown" have good biocompatibility. AuNRs entering the liver is located in lysosome of Kupffer cells in liver, which leads to lipid peroxidation in mice. Rely on the body's antioxidant defense system to return to normal.
【学位授予单位】：华南农业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R318.08;O614.123;TB383.1

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