Nanoparticle Surface Charge Directs the Cellular Binding of Nanoparticle-Protein Complexes

Abstract

Nanoparticles are commonly utilized in biological systems as imaging probes, drug delivery agents and in vivo sensors. In most biological applications, the nanoparticle is exposed to a complex mixture of extracellular proteins that adsorb non-specifically to the nanoparticle surface. The resulting “protein corona” can dominate the interactions of the nanoparticle with the cellular membrane. We have focused on the role of nanoparticle surface charge in the cellular binding of nanoparticles in the presence of extracellular proteins. Cationic, amine-modified polystyrene nanoparticles and anionic, carboxylate-modified polystyrene nanoparticles were studied as a model system. The cellular binding of cationic and anionic nanoparticles is distinctly different, determined from fluorescence microscopy experiments. For cationic nanoparticles, the cellular binding is increased in the presence of serum proteins. In comparison, anionic nanoparticle binding is inhibited by the presence of serum proteins. Competition assays performed with flow cytometry allowed us to quantify differences in binding and to identify the cellular receptors used by the nanoparticle-protein complexes. We have determined that complexes formed with anionic nanoparticles bind to native protein receptors, while those formed with cationic nanoparticles bind to scavenger receptors. These results indicate that for nanoparticles used in biological applications, the initial surface charge of the nanoparticle mediates cellular binding. Currently, we are extending our studies to nanoparticles used for drug and gene delivery.