Investigation on Active and Rapid Hepatobiliary Excretion of Triantennary N ‑Acetyl Galactosamine Conjugated Polymeric Nanoparticles

The current knowledge of hepatic lectin-specific N -acetylgalactosamine ligands is limited to the removal of glycoproteins/cells from circulation or targeting therapeutics to the liver. Here, we describe the influence of different N -acetylgalactosamine ligands conjugated to dendritic polymer-based therapeutic nanoparticles with sizes above the renal excretion limit on bypassing liver accumulation and their rapid excretion from the body. We determined that the chemistry, type, and presentation of sugar ligands on nanoparticles dictate their vascular retention, rapid intracellular hepatocyte transport, and the pathway of excretion. We further probed the mechanism of rapid hepatobiliary excretion in vivo using fluorescently labeled nanoparticles and found that the structure and characteristics of N -acetylgalactosamine ligands on the nanoparticle surface influence their interactions with different hepatic cells. The current study provides new directions and sheds light on better appraising design parameters that can be tailored for active hepatobiliary excretion of nanoparticles.