Monodisperse citrate-stabilized gold nanoparticles with a uniform quasi-spherical shape of up to ∼200 nm and a narrow size distribution were synthesized following a kinetically controlled seeded growth strategy via the reduction of HAuCl(4) by sodium citrate. The inhibition of any secondary nucleation during homogeneous growth was controlled by adjusting the reaction conditions: temperature, gold precursor to seed particle concentration, and pH. This method presents improved results regarding the traditional Frens method in several aspects: (i) it produces particles of higher monodispersity; (ii) it allows better control of the gold nanoparticle size and size distribution; and (iii) it leads to higher concentrations. Gold nanoparticles synthesized following this method can be further functionalized with a wide variety of molecules, hence this method appears to be a promising candidate for application in the fields of biomedicine, photonics, and electronics, among others.

In this work, we explore the formation of the protein corona after exposure of metallic Au nanoparticles (NPs), with sizes ranging from 4 to 40 nm, to cell culture media containing 10% of fetal bovine serum. Under in vitro cell culture conditions, zeta potential measurements, UV-vis spectroscopy, dynamic light scattering and transmission electron microscope analysis were used to monitor the time evolution of the inorganic NP-protein corona formation and to characterize the stability of the NPs and their surface state at every stage of the experiment. As expected, the red-shift of the surface plasmon resonance peak, as well as the drop of surface charge and the increase of the hydrodynamic diameter indicated the conjugation of proteins to NPs. Remarkably, an evolution from a loosely attached toward an irreversible attached protein corona over time was observed. Mass spectrometry of the digested protein corona revealed albumin as the most abundant component which suggests an improved biocompatibility.