Decoration of gold nanoparticles with glycopeptides leads to a lower cellular uptake and liver retention.

Unspecific uptake by the liver is one of the main drawbacks of the translation of nanomaterials into clinics, preventing their delivery into diseased tissues. Here, we synthesized gold nanoparticles (GNPs) decorated with a sialic acid-displaying glycopeptide to enhance their specific targeting properties by reducing their uptake inside hepatic cells. We demonstrated the biocompatibility of the glycopeptide-coated GNPs with two different nanomaterial shapes (spherical and rod-like GNPs) and the targeting properties of the glycopeptide were retained in serum-free and protein-rich media. We found that the glycopeptide reduces nanomaterial interaction with hepatic cells by 1.96 times. In the liver, Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) were the only cells that interacted with the GNPs, increasing the expression of sialic acid-binding receptors such as Siglec-1. This work provides potential new strategies to overcome off-target nanomaterial accumulation by manipulating nanomaterial functionalisation with glycans to alter hepatic cell interactions.