(76c) Electrostatic Nano-Assemblies on Nanoparticle Surfaces Direct Cell Interactions for Biomedicine

Over recent years, our lab has developed the use of electrostatic layer-by-layer (LbL) assembly as a means of modifying the surfaces of nanoparticles for biomedical applications. The nature of these alternating charge-based coatings is highly dependent on assembly conditions, polymer charge density, polyelectrolyte composition and molecular weight. We have demonstrated that the selection of the outer polyanion layer determines and impacts characteristics such as stealth properties, protein association, cellular interactions and even intracellular trafficking. The use of synthetic polypeptides, polysaccharides and native biomolecular systems can greatly influence the ability of these LbL nanoparticles to exhibit extended plasma half-life, penetrate tumor tissues, and target specific cell types including immune and tumor cells. We have developed simple electrostatic bilayer coatings that lead to high affinity to cancer cells while maintaining sufficiently low interactions with healthy cells to enable highly efficient tumor targeting. These systems can be designed to enhance transport across barriers such as the blood-brain barrier, properties that can be further enhanced through the complementary adsorption of additional targeting peptides of opposite charge. On the other hand, these nanolayered assemblies can be modified to modulate cell-particle interactions and facilitate transport through tissue while still enabling desirable specificity of cell association. Furthermore, it is possible to use these approaches to modify the uptake and transfection of mRNA lipid nanoparticles in a manner that enables a modular approach to targeting utilizing different polyelectrolytes. An overview of these approaches and their use to address ovarian cancer, glioblastoma and other biomedical applications will be discussed.