Zwitterionic glutathione monoethyl ester as a new capping ligand for ultrasmall gold nanoparticles

The natural tripeptide glutathione has become a popular choice for passivating the surface of gold nanoparticles (NPs) intended for in vivo applications. Here we investigate a zwitterionic derivative of glutathione - glutathione monoethyl ester - as a new capping ligand for ultrasmall NPs. The new zwitterionic particles (AuGSH(zwt)) were colloidally stable in biological media and resistant against binding from serum proteins. AuGSH(zwt), but not glutathione-coated particles, could be successfully functionalized with strep-tag II for binding specifically to target streptactin in the presence of serum proteins. Taken together, these results place AuGSH(zwt) as a promising choice for attaining simultaneous in vivo renal clearance and targeted delivery via incorporation of functional peptides. Ultrasmall gold nanoparticles coated with a zwitterionic derivative of glutathione are shown to be stable against aggregation and nonspecific binding from serum proteins.