The systematic evaluation of size-dependent toxicity and multi-time biodistribution of gold nanoparticles

Li, XM (Li, Xiaomin)^[ 1 ] ; Hu, ZP (Hu, Zhenpeng)^[ 1 ] ; Ma, JL (Ma, Jinlong)^[ 1 ] ; Wang, XY (Wang, Xinyu)^[ 1 ] ; Zhang, YP (Zhang, Yapei)^[ 1 ] ; Wang, W (Wang, Wei)^[ 1 ] ; Yuan, Z (Yuan, Zhi)^[ 1,2 ]

COLLOIDS AND SURFACES B-BIOINTERFACES, 2018, 167: 260-266

DOI: 10.1016/j.colsurfb.2018.04.005

 WOS:000434747200030

Abstract

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. (C) 2018 Elsevier B.V. All rights reserved.