Surface Charge-mediated Interactions and Transport of Ultrasmall Gold Nanoparticles in the Normal and Diseased Kidney

Fundamental understanding of the interactions and transport of nanoparticles in the normal and diseased kidney will provide a foundation for engineering the next generation of renal nanomedicine. Meanwhile, it can also provide insights to the renal physiology and the pathophysiology of renal diseases. To gain such a fundamental understanding requires us to correlate the physicochemical properties of nanoparticles with their interactions and transport in different renal segments at the tissue and the cellular levels. While the size-dependent intrarenal interaction and transport of nanoparticles has been well demonstrated over the past decades, how surface charge of nanoparticles can impact their interaction and transport in different renal segments remains less understood. This dissertation aims to unravel the surface charge-mediated interactions and transport of nanoparticles in the normal and diseased kidney. Chapter 1 of this dissertation reviews the current understanding of the interactions and transport of nanoparticles in different renal segments as well as the pathophysiology of different renal diseases associated to different renal segments. Chapter 2 describes the surface charge-mediated nano-bio interactions of ultrasmall gold nanoparticles in the normal kidneys at the tissue and the cellular levels in relation to the surface charge species and the spatial configuration of the terminal charge groups. Chapter 3 emphasizes on the correlation between the in vivo transport profiles and the intrarenal interactions of renal-clearable gold nanoparticles with different surface charge in both the normal and diseased kidney. Lastly, chapter 4 presents the summary and outlook. In this dissertation, we provide a clear picture of the surface charge-mediated interactions and transport of ultrasmall gold nanoparticles in the normal and diseased kidney at the tissue and the cellular levels. We believe this work can contribute to the design of renal nanomedicine for the diagnosis and treatment of kidney diseases and advance our fundamental understanding of the renal physiology and the pathophysiology of renal diseases.