Renally Excretable and Size-Tunable Silver Sulfide Nanoparticles for Dual-Energy Mammography or Computed Tomography

Significant effort has been focused on developing renally clearable nanoparticle agents since efficient renal clearance is important for eventual clinical translation. Silver sulfide nanoparticles (Ag₂S-NP) have recently been identified as contrast agents for dual-energy mammography, computed tomography (CT), and fluorescence imaging and probes for drug delivery and photothermal therapy with good biocompatibility. However, most Ag₂S-NP reported to date are not renally excretable and are observed in vivo to accumulate and remain in the reticuloendothelial system (RES) organs, i.e., liver and spleen, for a long time, which could negatively impact their likelihood for translation. Herein, we present renally clearable, 3.1 nm Ag₂S-NP with 85% of the injected dose (ID) being excreted within 24 h of intravenous injection, which is among the best clearance of similarly sized nanoparticles reported thus far (mostly between 20 and 75% of ID). The urinary excretion and low RES accumulation of these nanoparticles in mice were indicated by in vivo CT imaging and biodistribution analysis. In summary, these ultrasmall Ag₂S-NP can be effectively eliminated via urine and have high translational potential for various biomedical applications.