Blood protein coating of gold nanoparticles as potential tool for organ targeting
Blood protein coating of gold nanoparticles as potential tool for organ targeting
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DOI：
10.1016/j.biomaterials.2013.12.100
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发表时间：
2014-03-01
期刊：
影响因子：
14
通讯作者：
Krol, Silke
中科院分区：
文献类型：
--
作者：
Schaeffler, Martin;Sousa, Fernanda;Krol, Silke
纳米颗粒（NP）和纳米颗粒药物递送有望成为医学治疗的突破，但纳米毒性引起了人们的关注。我们提出了使用聚电解质多层包被的金NP（AuNP，核直径15和80 nm; Au-198放射性标记）的定量小鼠生物活性测定。在静脉内注射之前，这些与人血清白蛋白（alb-AuNP）或载脂蛋白E（apoE-AuNP）稳定缀合。我们比较了蛋白质-AuNP-缀合物与柠檬酸盐稳定的AuNP（cit-AuNP）的生物活性。使用15 nm双荧光标记的alb-AuNP-缀合物，在具有高AuNP含量的器官中用组织学补充生物标记。当与cit-AuNP相比时，蛋白质缀合大大降低了肝保留（在19小时和48小时时，alb-AuNP：52%，apoE-AuNP：72%，cit-AuNP：> 95%）。19 h时，蛋白偶联物在肺（alb-AuNP）和脾（alb-AuNP（16%），apoE-AuNP（21%））中的保留率分别为18%和21%。与cit-AuNP（对照）甚至apoE-AuNP相比，Alb-AuNP在肺部（因子：60（30分钟））中的分数显着增加; 111（19小时）; 235（48小时）和大脑（因子：70（30分钟））; 90（19小时）; >200（48小时）。与对照相比，蛋白质缀合对80 nm AuNP的生物分布的影响消失。在组织学上，15 nm的alb-AuNP在30 min后主要位于脑、肺、肝和肾的内皮中，而在19 h时它们移动到更深的实质中，例如在海马中。我们的研究清楚地表明，在静脉内给药之前，AuNP与白蛋白和apoE的稳定缀合增加了NP在患病靶器官中的特异性和效率，从而表明在纳米医学和纳米药理学中的潜在作用。(C)2014爱思唯尔有限公司版权所有。
Nanoparticles (NP) and nanoparticulated drug delivery promise to be the breakthrough for therapy in medicine but raise concerns in terms of nanotoxicity. We present quantitative murine biokinetics assays using polyelectrolyte-multilayer-coated gold NP (AuNP, core diameter 15 and 80 nm; Au-198 radiolabeled). Those were stably conjugated either with human serum albumin (alb-AuNP) or apolipoprotein E (apoE-AuNP), prior to intravenous injection. We compare the biokinetics of protein-AuNP-conjugates with citrate-stabilized AuNP (cit-AuNP). Biokinetics was complemented with histology in organs with high AuNP content using 15 nm double fluorescently-labeled alb-AuNP-conjugates. Protein conjugation massively reduced liver retention (alb-AuNP: 52%, apoE-AuNP: 72%, cit-AuNP: >95%, at 19 h and 48 h) when compared to cit-AuNP. The protein conjugates were retained in lungs (alb-AuNP (18%) and spleen (alb-AuNP (16%), apoE-AuNP (21%) at 19 h. Alb-AuNP show significantly increased fractions in lungs (factors: 60 (30 min); 111 (19 h); 235 (48 h) and brain (factors: 70 (30 min); 90 (19 h); >200 (48 h) compared to cit-AuNP (control) - or even to apoE-AuNP. The influence of protein conjugation on the biodistribution disappears for 80 nm AuNP comparing to control. Histologically, the 15 nm alb-AuNP are mainly located in the endothelium of brain, lungs, liver and kidneys after 30 min, while at 19 h they moved deeper into the parenchyma e.g. in hippocampus. Our study clearly suggests that stable conjugation of AuNP with albumin and apoE prior to intravenous administration increases specificity and efficiency of NP in diseased target-organs thus suggesting a potential role in nanomedicine and nanopharmacology. (C) 2014 Elsevier Ltd. All rights reserved.