Direct Conjugation of Resveratrol on Hydrophilic Gold Nanoparticles: Structural and Cytotoxic Studies for Biomedical Applications

Strongly hydrophilic gold nanoparticles (AuNPs), functionalized with citrate and L-cysteine, were synthetized and used as Resveratrol (RSV) vehicle to improve its bioavailability. Two different conjugation procedures were investigated: the first by adding RSV during AuNPs synthesis (1) and the second by adding RSV after AuNPs synthesis (2). The two different conjugated systems, namely AuNPs@RSV1 and AuNPs@RSV2 respectively, showed good loading efficiency (η%): η1 = 80 ± 5% for AuNPs@RSV1 and η2 = 20 ± 3% for AuNPs@RSV2. Both conjugated systems were investigated by means of Dynamic Light Scattering (DLS), confirming hydrophilic behavior and nanodimension (<2RH> 1 = 45 ± 12 nm and <2RH> 2 = 170 ± 30 nm). Fourier Transform Infrared Spectroscopy (FT-IR), Synchrotron Radiation induced X-Ray Photoelectron Spectroscopy (SR-XPS) and Near Edge X-ray Absorption Fine Structure (NEXAFS) techniques were applied to deeply understand the hooking mode of RSV on AuNPs surface in the two differently conjugated systems. Moreover, the biocompatibility of AuNPs and AuNPs@RSV1 was evaluated in the concentration range 1.0–45.5 µg/mL by assessing their effect on breast cancer cell vitality. The obtained data confirmed that, at the concentration used, AuNPs do not induce cell death, whereas AuNPs@RSV1 maintains the same anticancer effects as the unconjugated RSV.