Synthesis and Characterization of Thiolate-Protected Gold Nanoparticles of Controlled Diameter

Gold nanoparticles (AuNPs) have been the focus of many studies owing to their unique optical and electronic properties and versatile applications. However, synthesis of stable and homogeneous AuNPs with a particular choice of size is still a challenge. In this study we describe a direct synthesis approach to produce stable and monodisperse water-soluble AuNPs with a tightly controlled diameter in the 1.7–2.4 nm range. We controlled the size by changing only the sodium hydroxide (NaOH) concentration in the synthesis. Gel electrophoresis, transmission electron microscopy (TEM), and solution X-ray scattering showed that the AuNPs had narrow size-distributions. We further showed that AuNPs of the different sizes were clearly distinguishable in TEM micrographs, paving the way to dual-target labeling. The reactivity of the AuNPs toward DNA and proteins was also demonstrated. We utilized this reactivity to label tail-anchored proteins embedded in the membrane of the anticancer nanodrug Doxil as a means to target it to specific cell types. The gold-labeling enabled the precise localization of the tail-anchored proteins in cryo-TEM images of the therapeutic liposomes.