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

Abstract 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 m m 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.