In Situ Mineralization of Gold Nanoparticles from Sodium Aurothiomalate or Tetrachloroauric Acid in Human Cells

Abstract Biological systems can convert ionic gold precursors into nanoparticles (NPs) via redox-driven mineralization, yet the pathways and outcomes remain poorly understood. To address this, we investigated gold nanoparticle (Au NP) spontaneous formation from tetrachloroauric acid (HAuCl4) and sodium aurothiomalate (NaAuS) in mammalian cells and a complete cell culture medium. HAuCl4 underwent rapid multielectron reduction, producing abundant small intracellular NPs that, at higher concentrations, coalesced into compact clusters and compromised cell viability. In contrast, NaAuS followed slower one-electron reduction, was tolerated at higher concentrations, and yielded fewer but larger assemblies, including fibrous superstructures composed of crystalline Au domains. Extracellular mineralization generated morphologies distinct from those observed intracellularly, indicating that intracellular NPs result from cytoplasmic reduction rather than the uptake of extracellular products. Perturbations of the redox balance suppressed intracellular nucleation and promoted Au reduction in the extracellular milieu. Analysis of the NP size distributions provided mechanistic fingerprints: HAuCl4 produced narrow Gaussian-like profiles under synchronized nucleation, whereas NaAuS consistently generated broader log-normal distributions reflecting asynchronous growth. These findings demonstrate that the precursor and cellular redox state can be adjusted to control NP localization and morphology. Overall, this work links precursor chemistry and redox biology to NP architecture and highlights opportunities for biologically guided nanoparticle synthesis in imaging and therapeutic applications.