The Predictive Synthesis of Monodisperse and Biocompatible Gold Nanoparticles

The predictive bottom-up synthesis of monodisperse and biocompatible gold nanoparticles using seed-mediated growth procedures is limited by a lack of mathematical models relating reaction components to the final nanoparticle diameter. In this study, we used unique quantitative analytical methods at the single-nanoparticle level to identify the mathematical relationship between the moles of precursor ionic gold and the moles of nanoparticle seeds to synthesize monodisperse gold nanoparticles within ~5% of the target diameter in the ~10 to 120 nm size range. We investigated two commonly used gold nanoparticle syntheses, i.e., the formation of (i) citrate-coated, and (ii) cetyltrimethylammonium chloride (CTAC)-coated gold nanoparticles. Additionally, we developed a surface engineering approach using a physical replacement method that replaces cytotoxic CTAC with biocompatible citrate moieties. We confirmed the successful surface removal of CTAC using several analytical methods and demonstrated biocompatibility with cell viability tests. Our study provides tools and methods by which monodisperse and biocompatible gold nanoparticles can be predictably synthesized for potential downstream biomedical applications.