(442a) Polymer Nano-Assemblies for Bioresponsive Materials: From Macro- to Nano-Scale

Electrostatics, hydrogen bonding, and other secondary interactions enable the assembly of many novel materials systems from water.    By taking advantage of naturally occurring biomacromolecules in conjunction with well designed synthetic polymers, it is possible to use these interactions to build macromolecular assemblies that can present biologically relevant cues, both chemical and mechanical, to cells in vitro and in vivo to regulate their behavior.    Nanolayer assemblies generated by alternation of two or more complementary species, can be used to create designer biomaterials with the ability to encapsulate and controllably release sensitive biologic drugs such as active proteins and nucleic acids when exposed to various elements of the cellular or tissue environment.  We have adapted such systems to release antimicrobial peptides, growth factors that regulate bone growth and tissue generation, and siRNA that can block the expression of genes that regulate everything from wound healing to cancer cell survival.   Because these assemblies are thin and conformal, they can be applied on a very large scale to macroscopic surfaces such as tissue scaffolds, implants, or cellular substrates; however, they can also readily coat microscopic features and nanoparticles down to 10 to 20 nm in size.    By using the layered approach in these systems, it is possible to build films that contain different therapeutics in different regions of the film, which are released either together or in a staged, sequential fashion.   Using this approach, we have developed nanoparticles that can address cancer by first regulating a molecular or genetic pathway for cancer (essentially re-wiring the cell  network), followed by sustained release of chemotherapy or other drug treatments.  It is also possible to design “multilayer tattoos” that can be used for transdermal delivery of DNA vaccines, a method that can universally address a number of different disease types.   Finally, newer synthetic methods in our laboratory, including the generation of new clickable synthetic polypeptides that present the basis of new families of responsive biomaterials, and the use of rolling circle transcription to create poly-siRNA that can be assembled into nanostructures, and the resulting assembled systems will be discussed.