Defined Coadsorption of Prostate Cancer Targeting Ligands and PEG on Gold Nanoparticles for Significantly Reduced Protein Adsorption in Cell Media

A study on the surface chemistry of gold nanoparticles (AuNPs) utilizing gel electrophoresis is presented. The molecular design of targeting and stabilizing PEG ligands allows one to combine them in mixed ligand layers with control of relative composition. For all tested targeting and control ligands, coadsorption of PEG significantly reduces protein adsorption and matrix effects of cell media as compared to conjugates without PEG. Introducing carboxylic acid groups into the PEG ligand layer does not lead to increased protein adsorption as shown with carboxylic acid terminated PEG ligands. The controlled adsorption of PEG ligands with different molecular weights is used to disentangle the effects of particle charge and hydrodynamic diameter. Taken together, this study provides directions for the functionalization of nanoparticles to obtain conjugates which are well-defined in terms of composition and colloidally stable in complex media. This is in particular relevant for targeting applications and cell experiments.