Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China; Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
Colloids Surf B Biointerfaces. 2018 Jul 1;167:260-266. doi: 10.1016/j.colsurfb.2018.04.005. Epub 2018 Apr 4.
As a promising nanomaterial, gold nanoparticles (Au NPs) have been widely applied in diagnosis, drug and gene delivery, and photothermal therapy. However, the toxicity and biodistribution profile of differently sized Au NPs still remains controversial and incomplete, thus hindering their further applications. Herein, a systematic evaluation of size effect on toxicity and multi-time (from 4 h to 90 days) biodistribution of Au NPs ranging from 6.2 nm to 61.2 nm was conducted. The in vitro toxicity by MTT assays manifested that toxicity could be distinctly observed and increased with size decreasing when the dose of Au NPs reached up to a certain amount (1 mM). Subsequently, the corresponding toxicity mechanism was further studied via reactive oxygen species assay kit and the results indicated that Au NPs with various sizes would induce different oxidative stress which was accountable for the ultimate toxicity. Furthermore, the result of the biodistribution showed that Au NPs with larger sizes (42.5 and 61.2 nm) accumulated mainly in liver and spleen while little or none were found in heart, kidney and lung. Dissimilarly, smaller ones (6.2 and 24.3 nm) were distributed not only in liver and spleen but also in other organs. Additionally, most of the Au NPs were excreted out in less than 30 days, whereas there were still bits of remains in liver and spleen up to 90 days, especially for the 42.5 and 61.2 nm Au NPs. These findings are meaningful for the design of the Au NPs in the biomedical fields.
作为一种很有前途的纳米材料，金纳米粒子（Au NPs）已被广泛应用于诊断、药物和基因传递以及光热治疗。然而，不同尺寸的 Au NPs 的毒性和生物分布情况仍存在争议且不完整，从而阻碍了它们的进一步应用。在此，我们对尺寸效应对 Au NPs 毒性和多时间（4 小时至 90 天）生物分布的影响进行了系统评估，Au NPs 的尺寸范围为 6.2nm 至 61.2nm。MTT 测定的体外毒性表明，当 Au NPs 的剂量达到一定量（1mM）时，可明显观察到并随着尺寸的减小而增加毒性。随后，通过活性氧测定试剂盒进一步研究了相应的毒性机制，结果表明，不同尺寸的 Au NPs 会引起不同的氧化应激，这是导致最终毒性的原因。此外，生物分布的结果表明，较大尺寸（42.5nm 和 61.2nm）的 Au NPs 主要在肝脏和脾脏中积累，而在心脏、肾脏和肺部中则很少或没有发现。相反，较小尺寸（6.2nm 和 24.3nm）的 Au NPs 不仅在肝脏和脾脏中分布，而且在其他器官中也有分布。此外，大多数 Au NPs 在 30 天内被排出体外，而在 90 天内仍有少量残留在肝脏和脾脏中，尤其是对于 42.5nm 和 61.2nm 的 Au NPs。这些发现对于生物医学领域 Au NPs 的设计具有重要意义。
