Thiol-Mediated Multidentate Phosphorylcholine as a Zwitterionic Ligand for Stabilizing Biocompatible Gold Nanoparticles.

The increasing application of gold nanoparticles (AuNPs) in biomedicine requires extensive investigation of surface modification and stabilization to maximize their advantages for the diversity of more challenging biological utilization. Herein, a thiol-mediated multifunctional phospholipid ligand was designed while disclosing a zwitterionic nature to AuNPs. The ligand was synthesized by attachment to two bidentate lipoic acid (LA) anchor groups and incorporation of a zwitterionic phosphatidylcholine (PC) group, allowing for excellent hydrophilicity. As demonstrated through ultraviolet-visible spectroscopy, appropriate 7 nm diameter AuNPs modified with a 1,2-dilipoyl-sn-glycero-3-phosphorylcholine (di-LA-PC) compact ligand exhibited the best colloidal stability in a high NaCl concentration of up to 217 mM, different temperatures, and a wide range of pH values from 3 to 11 when compared to the traditional surfactants or thiol-contained amino acid surface modification cases. These AuNPs are also stable without specific interaction to positively/negatively charged proteins, possibly leading to prolonged blood circulation after in vivo administration. Moreover, much more resistance to ligand competition of dithiothreitol was found than other thiol-coated AuNPs, which further highlighted their affinity in an aqueous system. Biocompatibility of the zwitterionic ligand di-LA-PC-modified AuNPs was finally evaluated by hemolysis and cytotoxicity tests. Cumulatively, the remarkable stability and biocompatibility of AuNPs, multicoordinated with a di-LA-PC ligand, potentially motivated them as a practical alternative for surface tailoring in biotechnology.