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Systematic in vitro toxicological screening of gold nanoparticles designed for nanomedicine applications

机译:设计用于纳米医学的金纳米颗粒的系统体外毒理学筛选

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摘要

Gold nanoparticles (AuNP) are increasingly being applied in the biomedical field as therapeutics, contrast agents, and in diagnostic systems, motivating investigations of their toxicity that might arise from accidental exposure. While other work has investigated the toxicological response to gold nanoparticles for industrial purposes, here we have surveyed formulations that have been developed for biomedical use, are in clinical trials or have been FDA-approved. The AuNP library tested contains a range of shapes, inculding spheres, rods and shells, that possess a range of coatings, such as silica, citrate, lipoprotein, polymaleic acid, polyethylene glycol, DNA and others. Good cytocompatibility for all formulations was observed after 1 hour of incubation. However after 24 hours exposure, a nanorod and a spherical DNA coated formulation resulted in toxicity. The coating material was the only factor that influenced toxicity. AuNP exposure seemed to have no effect on cell cytoskeleton deformation and cell spreading. Cell uptake, as measured by computed tomography and ICP-OES, as well as TEM images of cells, confirmed strong AuNP uptake for certain formulations, but there was no correlation with toxicity. No glove translocation occurred, therefore, nitrile gloves are an adequate safety precaution for working with the AuNP studied. In conclusion, the majority of AuNP formulations tested have very low adverse effects.
机译:金纳米颗粒(AuNP)越来越多地在生物医学领域用作治疗剂,造影剂和诊断系统,从而激发了人们对因意外接触而产生的毒性进行研究的动机。尽管其他工作已经调查了工业目的对金纳米颗粒的毒理学响应,但在这里我们已经调查了已开发用于生物医学用途,正在临床试验中或已获得FDA批准的制剂。经过测试的AuNP库包含一系列形状,镶嵌球,棒和壳,它们具有一系列涂层,例如二氧化硅,柠檬酸盐,脂蛋白,聚马来酸,聚乙二醇,DNA等。温育1小时后,观察到所有制剂的良好细胞相容性。但是,暴露24小时后,纳米棒和球形DNA涂层制剂会产生毒性。涂料是影响毒性的唯一因素。 AuNP暴露似乎对细胞骨架变形和细胞扩散没有影响。通过计算机断层扫描和ICP-OES测量的细胞摄取以及细胞的TEM图像证实了某些制剂对AuNP的强烈摄取,但与毒性没有相关性。没有发生手套移位,因此,丁腈手套是研究AuNP的充分安全预防措施。总之,测试的大多数AuNP制剂的不良反应非常低。

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