Multiplexable and Scalable Aqueous Synthesis Platform for Oleate-Based, Bilayer-Coated Gold Nanoparticles

Despite gold-based nanomaterials having a unique role in nanomedicine, among other fields, synthesis limitations relating to reaction scale-up and control result in prohibitively high gold nanoparticle costs. In this work, a new preparation procedure for lipid bilayer-coated gold nanoparticles in water is presented, using sodium oleate as reductant and capping agent. The seed-free synthesis not only allows for size precision (8-30 nm) but also remarkable particle concentration (10 mm Au). These reaction efficiencies allow for multiplexing and reaction standardization in 96-well plates using conventional thermocyclers, in addition to simple particle purification via microcentrifugation. Such a multiplexing approach also enables detailed spectroscopic investigation of the nonlinear growth process and dynamic sodium oleate/oleic acid self-assembly. In addition to scalability (at gram-level), resulting gold nanoparticles are stable at physiological pH, in common cell culture media, and are autoclavable. To demonstrate the versatility and applicability of the reported method, a robust ligand exchange with thiolated polyethylene glycol analogues is also presented.