Systematic and mechanistic analysis of AuNP-induced nanotoxicity for risk assessment of nanomedicine

For decades, nanoparticles (NPs) have been widely implemented in various biomedical fields due to their unique optical, thermal, and tunable properties. Particularly, gold nanoparticles (AuNPs) have opened new frontiers in sensing, targeted drug delivery, imaging, and photodynamic therapy, showing promising results for the treatment of various intractable diseases that affect quality of life and longevity. Despite the tremendous achievements of AuNPs-based approaches in biomedical applications, few AuNP-based nanomedicines have been evaluated in clinical trials, which is likely due to a shortage of understanding of the biological and pathological effects of AuNPs. The biological fate of AuNPs is tightly related to a variety of physicochemical parameters including size, shape, chemical structure of ligands, charge, and protein corona, and therefore evaluating the effects of these parameters on specific biological interactions is a major ongoing challenge. Therefore, this review focuses on ongoing nanotoxicology studies that aim to characterize the effect of various AuNP characteristics on AuNP-induced toxicity. Specifically, we focus on understanding how each parameter alters the specific biological interactions of AuNPs via mechanistic analysis of nano-bio interactions. We also discuss different cellular functions affected by AuNP treatment (e.g., cell motility, ROS generation, interaction with DNA, and immune response) to understand their potential human health risks. The information discussed herein could contribute to the safe usage of nanomedicine by providing a basis for appropriate risk assessment and for the development of nano-QSAR models.