Biological Interaction and Imaging of Ultrasmall Gold Nanoparticles

Ultrasmall gold nanoparticles (AuNPs) typically includes atomically precise gold nanoclusters (AuNCs) and AuNPs with a core size below 3 nm. Serving as a bridge between small molecules and traditional inorganic nanoparticles, the ultrasmall AuNPs show the unique advantages of both small molecules (e.g., rapid distribution, renal clearance, low non-specific organ accumulation) and nanoparticles (e.g., long blood circulation and enhanced permeability and retention effect). The emergence of ultrasmall AuNPs creates significant opportunities to address many challenges in the health field including disease diagnosis, monitoring and treatment. Since the nano–bio interaction dictates the overall biological applications of the ultrasmall AuNPs, this review elucidates the recent advances in the biological interactions and imaging of ultrasmall AuNPs. We begin with the introduction of the factors that influence the cellular interactions of ultrasmall AuNPs. We then discuss the organ interactions, especially focus on the interactions of the liver and kidneys. We further present the recent advances in the tumor interactions of ultrasmall AuNPs. In addition, the imaging performance of the ultrasmall AuNPs is summarized and discussed. Finally, we summarize this review and provide some perspective on the future research direction of the ultrasmall AuNPs, aiming to accelerate their clinical translation.