In vivo toxicity, biodistribution, and clearance of glutathione-coated gold nanoparticles

Gold nanoparticles are emerging as promising materials from which to construct nanoscale therapeutics and therapeutic delivery systems. However, animal studies have shown that gold nanoparticles modified with certain thiol monolayers such as tiopronin can cause renal complications and morbidity. Although these effects may be eliminated by coadsorbing small amounts of polyethylene glycol (PEG) onto the nanoparticle surface, PEG can also lower cellular internalization efficiency and binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics. Using ICP-MS analysis of blood, urine, and several organs, we show in this article that glutathione-coated gold nanoparticles (1.2 nm ± 0.9 nm) cause no morbidity at any concentration up to and including 60 μM and target primary organs although providing gradual dissipation and clearance over time. This study suggests that glutathione may be an attractive alternative to PEG in the design of gold nanoparticle therapeutics.From the Clinical EditorThis study describes the utility and toxicity of glutathione coated gold nanoparticles in comparison to PEGylated counterparts that are commonly used to increase “Stealth” properties and lower cytotoxicity. Too much PEG on the NPs can lead to lower cellular internalization efficiency and less efficient binding interactions with protein disease targets, significantly reducing the potential for using gold nanoparticles as therapeutics.

Graphic AbstractThe biodistribution and clearance of glutathione-coated gold nanoparticles shows efficient clearance through the urinary filtration system, a 100% survival rate, and no adverse histological pathology at concentrations up to and including 60 μM after subcutaneous administration. This efficient clearance combined with sufficient organ targeting make glutathione-coated gold nanoparticles a potentially viable candidate for future in vivo applications.Figure optionsDownload high-quality image (67 K)Download as PowerPoint slide