Effect of surface charge and ligand organization on the specific cell-uptake of uPAR-targeted nanoparticles

The decoration of nanoparticle surfaces with receptor-specific ligands can improve the delivery of their therapeutic load to cancer cells. Using as the ligand, U11, a peptide specific for the cancer-associated urokinase plasminogen activator receptor, we examined the effect of manipulation of nanoparticle properties on the targeting specificity of U11-nanoparticles. The nanoparticle surface charge was controlled by varying the amount of the cationic lipid within the nanoparticle formulation. A reduction in surface charge led to an increase in the targeting effect of U11-nanoparticles, a result of limiting its non-specific interactions with negatively charged cellular membranes. Furthermore, fluorescence and circular dichroism spectroscopy were used to probe changes in the U11 presentation on the surfaces of nanoparticles. Optimized ligand conformations were when ligands were separated into monomers and protruded from the nanoparticle surface. It is concluded that both the ligand organization as well as the nanoparticle platform require control to give optimal cell uptake efficiencies.