Stealth and biocompatible gold nanoparticles through surface coating with a zwitterionic derivative of glutathione

Abstract

Gold nanoparticles (AuNPs) hold promise in biomedi-cine, but challenges like aggregation, protein corona formation, andinsufficient biocompatibility must be thoroughly addressed beforeadvancing their clinical applications. Designing AuNPs with specificprotein corona compositions is challenging, and strategies for coronaelimination, such as coating with polyethylene glycol (PEG), havelimitations. In this study, we introduce a commercially availablezwitterionic derivative of glutathione, glutathione monoethyl ester(GSHzwt), for the surface coating of colloidal AuNPs. Particles coatedwith GSHzwt were investigated alongside four other AuNPs coated withvarious ligands, including citrate ions, tiopronin, glutathione, cysteine,and PEG. We then undertook a head-to-head comparison of theseAuNPs to assess their behavior in biological fluid. GSHzwt-coated AuNPsexhibited exceptional resistance to aggregation and protein adsorption. The particles could also be readily functionalized with biotinand interact with streptavidin receptors in human plasma. Additionally, they exhibited significant blood compatibility andnoncytotoxicity. In conclusion, GSHzwt provides a practical and easy method for the surface passivation of AuNPs, creating “stealth”particles for potential clinical applications.