(432c) Designer Nanoplexes for Delivery to Targeted Tissues

Authors: 
The generation of LbL nanoparticles that can directly target a specific tissues such as metastatic tumors, the lungs, or other key organs is dependent on the nature of the outer LbL layer, and the biodistribution of the nanoparticle is highly dependent on net surface charge, degree of hydration, and type of polyelectrolyte bilayer pair that is adsorbed as the final layers on the nanoparticle. Recent work in which these nanoparticle systems are designed for optimized uptake by advanced serous ovarian cancer cells will be discussed, and the use of these approaches to deliver combination siRNA/chemotherapy or drug inhibitor combination therapies or to generate imaging systems and theranostic nanoparticles will be addressed. The potential to target other tissues using designed nanoplex systems is discussed, in particular for the case of targeting cartilage to address the early stages of post-traumatic osteoarthritis. The manipulation of outer surface charge and polymer chain functionality, as well as the ability to design these layered nanoscale complexes to respond to micro-environment cues to achieve controlled biodistribution and uptake to targeted cells in vivo will be described. Finally, the layer-by-layer approach can be used to generate finely tuned release surfaces that can release small molecule, proteins, nucleic acids and other biologic drugs over sustained time periods, and with significant control of release characteristics. This approach is particularly attractive for the delivery of proteins and nucleic acids such as siRNA. New polyplexes designed to complex mRNA with its capping protein, or siRNA with the Ago2 component of the RISC complex combine protein and RNA in stabilized complexes that greatly enhance translation, and exhibit promise for treatments including cancer vaccines.