Interactions of Renal Clearable Gold Nanoparticles with the Kidneys in Vitro and in Vivo
The emergence of renal clearable inorganic nanoparticles (NPs) offers a great opportunity to address the health concern raised by nonspecific accumulation of conventional inorganic NPs in the macrophage system, mostly in the liver and spleen. In recent decades, we have dedicated a remarkable amount of research in developing renal clearable gold nanoparticles (AuNPs) and investigating their biointeractions. Our group discovered that glutathione-coated renal clearable AuNPs (GS-AuNPs) can be efficiently excreted through the urinary system resulting in significantly reduced accumulation in the liver and spleen. By integrating the near-infrared fluorescence, GS-AuNPs can sensitively probe kidney clearance kinetics and indicate renal dysfunction. Future clinical translation requires a fundamental understanding of nano-bio interactions in the kidneys and the biocompatibility of GS-AuNPs. In this dissertation, Chapter 1 covers the status of renal clearable inorganic NPs and the current understanding of their biointeractions in the kidneys. Chapter 2 describes using X-ray imaging to visualize the transport of GS-AuNPs in the kidney components under both normal and pathological conditions. The unique deposition of GS-AuNPs in the diseased kidney offers a great chance to diagnose renal injury noninvasively. Chapter 3 focuses on the blood transport and biocompatibility of GS-AuNPs. The dose effect on the blood transport and renal clearance efficiency of GS-AuNPs is unraveled which results in high biocompatibility. Chapter 4 describes an in vitro study on the surface-ligand-density effect on interactions between GS-AuNPs and human kidney proximal tubular cells. The results demonstrate precise responses of proximal tubular cells to GS-AuNPs with different ligand densities in membrane affinity, cytotoxicity and the mechanism of cell death. Finally, a summary of the obtained understanding and future perspective are presented in Chapter 5.