Role of gold nanoparticles capping density on stability and surface reactivity to design drug delivery platforms

Five-nanometer sized gold nanoparticles (Au NPs) stabilized with citrate ions have been reacted with various amounts of dihydrolipoic acid (DHLA) (×28, ×56, ×140, ×222, relative to Au NPs). Ligand exchange between citrate and the dithiol resulted in DHLA-capped Au NPs, whose degree of inertia was found to be related to the density of capping. The results revealed the importance of DHLA coating density to enhance the colloidal stability and modulate the reactivity toward free radicals and proteins of biological relevance. Thus, Au NPs capped with the highest amount of DHLA were found to be the ones that were, first, the most resistant to environmental changes, then characterized by the lowest residual catalytic reactivity of their metallic core, and finally the lowest interacting with proteins through nonspecific adsorption. The physicochemical properties conferred to Au NPs prepared with the ×222 excess should be valuable for further pharmaceutical development of nanoparticle platforms.