Elimination Pathways of Nanoparticles

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.

Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles

“…Collectively, we have observed distinctive biodistribution routes among l ‐, d ‐, and dl ‐G@SeNPs. The distribution of the l ‐G@SeNPs in the liver, kidneys, and intestines was consistent with those commonly reported . However, the d ‐G@SeNPs and dl ‐G@SeNPs escaped from the hepatobiliary pathway and suffered a faster renal clearance than the naturally existing l ‐G@SeNPs, which might be due to the lower cell adhesion of d ‐GSH with biological components, i.e., plasma membranes, proteins, and corona from different organs and blood constituents .…”

“…Intravenously administered nanoparticles are cleared from the body through two main pathways: hepatobiliary elimination and renal elimination . To identify whether nanoparticles with different chirality exhibit distinct biodistributions, PET scans were conducted with radiolabeled nanoparticles.…”

Ultra-small bimetallic iron–palladium (FePd) nanoparticle loaded macrophages for targeted tumor photothermal therapy in NIR-II biowindows and magnetic resonance imaging

“…What's more, the ultra-small size (<6 nm) of nanoparticles let it be eliminated renally. 24 Therefore, FePd NPs are a biocompatible nanomaterial. However, nanoparticles such a small size range (<20 nm) are rapidly aggregated in blood, passivated by serum protein adsorption onto the nanoparticle surfaces, losing therapeutic potentials.…”

Chirality‐Driven Transportation and Oxidation Prevention by Chiral Selenium Nanoparticles

“…Intravenously administered nanoparticles are cleared from the body through two main pathways: hepatobiliary elimination and renal elimination. [18] To identify whether nanoparticles with different chirality exhibit distinct biodistributions, PET scans were conducted with radiolabeled nanoparticles. For radiolabeling, the chiral G@SeNPs were coupled with 64 Cu through the linkage of p-SCN-Bn-NOTA at pH 5.5 (Figure 2 a, I).…”

“…The distribution of the l-G@SeNPs in the liver, kidneys, and intestines was consistent with those commonly reported. [18] However, the d-G@SeNPs and dl-G@SeNPs escaped from the hepatobiliary pathway and suffered a faster renal clearance than the naturally existing l-G@SeNPs, which might be due to the lower cell adhesion of d-GSH with biological components, i.e., plasma membranes, proteins, and corona from different organs and blood constituents. [1a, 23] Especially, the fact that the renal localization of dl-G@SeNPs is stronger than that of the d-counterpart was ascribed to its neutral charge and steric conformation, which facilitated the electrostatic interaction with the kidney, and reduced the opsonization to retard the sequestration by MPS.…”