Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles.

Abstract

BACKGROUND:

Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated.

PURPOSE:

The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo.

RESULTS:

Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs  but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice.

CONCLUSION:

Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.

• Authors: Qiyue Xia, Jinxing Huang, Qiyi Feng, Xuanming Chen, Xinyi Liu, Xiaojie Li, Ting Zhang, Shuwen Xiao, Hongxia Li, Zhihui Zhong, Kai Xiao
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 14 Pg. 6957-6970 ( 2019) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 32021157 (Publication Type: Journal Article)
• Copyright: © 2019 Xia et al.

Chemical References

• Cytokines
• Reactive Oxygen Species
• Gold
• CASP3 protein, human
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cytokines (metabolism)
• Gold (pharmacology)
• Hemolysis (drug effects)
• Hep G2 Cells
• Humans
• Metal Nanoparticles (adverse effects, chemistry)
• Mice
• Mice, Inbred BALB C
• Particle Size
• Reactive Oxygen Species (metabolism)
• Tissue Distribution
• Toxicity Tests