Prof. Christine Payne, Georgia Tech

AACP Seminar Series

Cellular Internalization and Transport of Nanoparticles

Nanoparticles have important biomedical applications ranging from gene therapy to cellular imaging. In each case, the nanoparticle must be functionalized for cellular delivery and targeting. Functionalization for cellular delivery has focused on cationic polymers, lipids, and peptides that bind to anionic receptors on the cell surface for internalization by the cell. While the picture of cationic ligands interacting with anionic receptors is conceptually straightforward, recent research has shown that nanoparticles bind to extracellular serum proteins resulting in anionic nanoparticles that are effectively coated with these proteins. This effect appears to be common to many types of nanoparticles with a range of different ligands. Current research in the Payne Lab focuses on the cellular binding and internalization of nanoparticles in the presence of serum proteins that mimic the in vivo environment. Using two-color fluorescence microscopy and single particle tracking we have measured the colocalization of serum proteins and nanoparticles upon binding to the cell surface and during cellular uptake. We find that initial binding to the cell surface occurs as a protein-nanoparticle complex and that displacement of the serum proteins from the NP is dependent on the type of serum protein. Similarly, extracellular serum proteins remain bound to the NP during internalization and are retained in the same endocytic vesicles over a period of at least 1 hr. These results demonstrate that serum proteins may be a dominating factor in nanoparticle-cell interactions and must be carefully considered in the rational design of nanoparticles for cellular delivery.