(119b) Layer-By-Layer Nanoparticles As Multi-Functional Delivery Systems

Layer-by-Layer (LbL) assembly is a highly tunable, modular approach to surface-limited functionalization of materials with nanoscale precision over the composition and properties of the film components. This high level of control affords the capability to design systems that are multi-functional in nature, with temporal and spatial control over the release of a diverse range of materials and therapeutics of interest. Surface-mediated interactions are of particular interest in biological settings where this interface between delivery systems and cells/biological environment govern binding and internalization on a cellular level and the pharmacokinetic properties of the system at a higher level in vivo. Application of this approach to nanomedicine has been successful in designing hydrated, protein-resistive long-circulating nanoparticles, as well as systems that shed a hydrated shell used for enhanced persistence in the bloodstream and EPR-based accumulation in the hypoxic tumor microenvironment, whereby exposure of a positively-charged material facilitates rapid uptake by tumor cells. This has driven much interest in further characterizing these systems as drug carriers, with the means to sustain drug in complex biological settings, such as the bloodstream. Using a two-color in vivo imaging approach, the biological performance of drug-loaded LbL nanoparticles was evaluated, affording us the capability to screen a library of material systems to rapidly evaluate them as systemic therapeutic carriers. This approach has further allowed us to conceive of systems that provide a means for cellular recognition by incorporation of a targeting ligand, as well as ones that are capable of programmable release of synergistic combinations of drugs for enhanced efficacy in invasive cancer cell types.