Rapid Tubular Accumulation of Renal-Clearable Gold Nanoparticles Enhances Computed Tomography Contrast Imaging of the Kidneys

Renal-clearable gold nanoparticles (RC-AuNPs) show promise for kidney computed tomography (CT) imaging by providing structural and functional information. To aid their clinical translation, understanding how their physicochemical properties affect renal CT enhancement is essential. By a head-to-head comparison of glutathione-coated and PEGylated RC-AuNPs (GS-AuNPs and PEG-AuNPs, respectively), we found that while PEG-AuNPs were renally cleared, their slower tubular entry at the early phase led to their suboptimal renal enhancement. Moreover, although surface folate modification enhanced RC-AuNP renal accumulation via actively targeting folate receptors on the tubular epithelium, their slower transport into tubules weakened renal enhancement. The effective renal CT enhancement by RC-AuNPs was not determined by their overall renal accumulation efficiency, but by their rapid entry into tubules, which can be reflected by their kidney:blood ratio 10 min after administration. Our work highlighted the superior performance of zwitterionic RC-AuNPs and provided design guidelines for developing better renal CT contrast agents.