Intracellular Biotransformation of Engineered Ultrasmall Gold Nanoparticles in Aurosomes

The aurosome, a concept introduced half a century ago, refers to intracellular vesicles that contain gold-based materials. The widespread clinical use of gold salts for the treatment of rheumatoid arthritis, together with advances in ultramicrotomy and biological transmission electron microscopy (TEM) in the 1970s, stimulated investigations into the deposition of gold salts in synovial tissues. These studies revealed a distinctive intracellular biotransformation process in which gold salts were converted within lysosomes into flower-like nanostructures composed of assembled nanofibers; these lysosomes were consequently termed aurosomes. However, research on aurosomes remained largely dormant for nearly four decades as more effective therapeutics replaced gold salts in clinical practice. In recent years, aurosomes have re-emerged following discoveries that ultrasmall (< 3 nm) engineered gold nanoparticles (AuNPs) undergo intracellular biotransformation similar to that of gold salts. These findings highlight the profound alterations in nanoparticle physicochemical properties induced by interactions with the complex intracellular environment. Moreover, fundamental studies on the biotransformation of ultrasmall AuNPs have advanced our understanding of their in vivo fate and expanded their potential biomedical applications. In this review, we revisit the historical development of aurosomes, summarize current research on aurosomes derived from ultrasmall AuNPs, and offer perspectives on future directions in this field.