Au Nanoparticle Synthesis in the Presence of Thiolated Hyaluronic Acid

Gold nanoparticles (AuNPs) are of significant interest due to their unique properties and applications in biomedicine. While hyaluronic acid (HA) has been used to modify pre-formed AuNPs, its thiolated derivative (HA-SH) has been less explored for the direct synthesis and stabilization of AuNPs. This study investigates the use of thiolated hyaluronic acid as a key component in the synthesis of AuNPs. A series of HA-AuNPs (HA-AuNP1-4) were synthesized by reacting HA-SH with HAuCl₄ at different mass ratios. The resulting nanoparticles were characterized using UV-Vis spectroscopy, scanning/transmission electron microscopy (SEM/STEM), X-ray photoelectron spectroscopy (XPS), photon cross-correlation spectroscopy (PCCS), and zeta potential measurements. The chemical transformations of the thiol ligand were studied using NMR spectroscopy. The morphologies and sizes of AuNPs depended on the HA-SH-to-HAuCl₄ ratio, ranging from icosahedral and triangular particles (≥146 nm) to quasi-spherical particles with a bimodal distribution (6-7 nm and 45-60 nm). XPS confirmed the presence of metallic gold (Au⁰) and a Au-S bond, while NMR and XPS revealed the partial oxidation of thiol groups to sulfonic acid. Zeta potential measurements showed that lower HAuCl₄ concentrations resulted in higher negative charge (up to -41.5 mV), enhancing colloidal stability. This work demonstrates a versatile approach to the synthesis of hyaluronic acid-based gold nanomaterials with tunable properties for potential biomedical applications.