Elimination Pathways of Nanoparticles

TLDR

Nanoparticle elimination is essential for clinical translation, yet large nonbiodegradable particles cannot be cleared renally and rely on poorly understood hepatobiliary pathways involving multiple cellular compartments that can sequester or modify them. The study investigated the barriers governing hepatobiliary elimination of nanoparticles. The authors found that liver nonparenchymal cells dictate elimination fate, with Kupffer cell depletion boosting fecal excretion over tenfold, and their data, together with previous work, enable a systematic view of how particle size and design influence elimination pathways.

Abstract

Understanding how nanoparticles are eliminated from the body is required for their successful clinical translation. Many promising nanoparticle formulations for in vivo medical applications are large (>5.5 nm) and nonbiodegradable, so they cannot be eliminated renally. A proposed pathway for these nanoparticles is hepatobiliary elimination, but their transport has not been well-studied. Here, we explored the barriers that determined the elimination of nanoparticles through the hepatobiliary route. The route of hepatobiliary elimination is usually through the following pathway: (1) liver sinusoid, (2) space of Disse, (3) hepatocytes, (4) bile ducts, (5) intestines, and (6) out of the body. We discovered that the interaction of nanoparticles with liver nonparenchymal cells (e.g., Kupffer cells and liver sinusoidal endothelial cells) determines the elimination fate. Each step in the route contains cells that can sequester and chemically or physically alter the nanoparticles, which influences their fecal elimination. We showed that the removal of Kupffer cells increased fecal elimination by >10 times. Combining our results with those of prior studies, we can start to build a systematic view of nanoparticle elimination pathways as it relates to particle size and other design parameters. This is critical to engineering medically useful and translatable nanotechnologies.