In vivo analyses of embryotoxicity and teratogenicity of gold nanoparticles: Emphasis on the surface chemistry and toxicological responses

The surface chemistry and physical characteristics of gold nanoparticles (AuNPs) influence their biological interactions and toxicological responses. However, the toxicological effects of surface charge on embryonic development remain poorly understood. In this study, we investigated the in vivo developmental toxicity and teratogenicity of differentially charged AuNPs during early embryogenesis of Xenopus laevis - a sensitive and ecologically relevant animal model for developmental toxicology. Our study indicated that cationic AuNPs induced significant embryotoxicity and teratogenicity including lethality, phenotypical abnormalities and disruption of gene expression associated with liver, digestive tract, neural, and eye development. In contrast, such effects, including lethality and malformations associated with changes in gene expression were not observed in embryos exposed to anionic AuNPs. In addition, cationic AuNPs affected ciliogenesis by reducing the number of multiciliated cells and disturbing cilia-driven fluid flow, a critical endpoint in nanoparticle-induced toxicity. Furthermore, gene expression profiles suggested that necroptosis might be the mechanism of cell death in embryos exposed to cationic AuNPs. Notably, the surface charge dependent AuNPs exposure leading to impaired ciliogenesis and activation of necroptosis during embryogenesis represents significant endpoints in nanotoxicology. Unlike previous studies focusing on zebrafish or rodents, this study provides the first systematic evaluation in X. laevis embryos with identical nanoparticle cores but distinct surface chemistries. Our study underscores the significance of nanoparticle surface functionalization in determining developmental toxicity and pinpoints the ecological risks imposed by cationic AuNPs during early embryonic development in aquatic systems.