Exploration of surface chemistry effects on the biodistribution and pharmacokinetics of dual-ligand luminescent gold nanoparticles

Understanding how surface chemistry influences gold nanoparticle (AuNP) biodistribution and pharmacokinetics is critical for the design of Au-based nanoprobes for in vivo sensing and imaging. AuNPs prepared using a single surface ligand have been widely studied; however, limited work has been reported for luminescent AuNPs decorated with multiple surface ligands. Herein, we describe the synthesis and characterization of four dual-ligand luminescent AuNPs prepared using a combination of four thiol-containing ligands (GSH, MUA, tDK, tDY). The impact of surface chemistry on in vivo biodistribution and pharmacokinetics was then investigated for each dual-ligand AuNP type using a mouse model. Our results indicate that variation of one of the two surface ligands can exert a significant influence on the pharmacokinetics and biodistribution of the AuNPs. Interestingly, we observed changes in biodistribution in the lung and digestive organs, as well as blood circulation time. These results are expected to inform the future de novo design of dual-ligand luminescent AuNPs for in vivo applications.