An interesting nanodrug delivery system is polyelectrolyte multilayer-coated nanogold. For better understanding of the binding of polycations or the counter-indicative deposition of polyanions on the citrate-stabilized gold nanoparticles, we used a surface-enhanced Raman spectroscopy to characterize the orientation of the polyions towards the gold surface. It was found that poly-allylamine replaces citrate molecules while the polyanion, poly-styrene sulfonate, intercalates in the citrate shell. One of the major obstacles for polyelectrolyte-coated nanogold is its tendency to agglomerate in the presence of high ion concentration as present, e.g., in blood. A novel encapsulation protocol for polyelectrolyte multilayer coating of gold nanoparticles was developed to successfully overcome this drawback. Moreover, electrostatic functionalization of the polyelectrolyte shell with a model target molecule for cancer, folic acid, induced a significant increase in the particle uptake in folate-receptor over-expressing breast cancer cell lines, VP 229 and MDA MB 231, compared to non-targeted particles or cells (non-activated macrophages) not expressing the folate receptor.
