(420d) Tuning Stickiness on Polyelectrolyte Nanocarriers to Target Cells and Tissues

Polyelectrolytes have unique properties that make them advantageous for the design of nanomaterials for drug delivery. These polymers are water-soluble, have a large number of easily modified reactive side chains for attachment of ligands, and can exhibit charge that can be designed to be sensitive to physiological conditions such as pH, redox conditions or the presence of specific enzymes. This capability makes charge a very enabling tool in the targeting of nanoparticles to specific tissues, as well as in adapting the transport of nanoparticles through the tissue matrix. Furthermore, certain cells may also be more effectively targeted through the presentation of charge alone or in combination with moieties that introduce more specific interactions. In each case in which charge is a factor, there is also a complementary requirement to modulate the charge to enable interaction while affording effective diffusion and transport within tissues and organs. Examples include the use of charged polyamidoamine dendrimers for the penetration of drug into cartilage, and the use of polyethylene oxide shielding groups to modify the amount of charge exposed. Similarly, nanoparticles may be adapted to penetrate viscous barriers such as bacteria biofilm, but must exhibit an ability to modulate charge to enable attractive interactions without preventing significant uptake. Ultimately, it is also important to introduce other kinds of polyelectrolyte interactions, particularly when targeting specific cells such as immune or cancer cells; often these interactions include recepter-specific interactions, but non-specific interactions can also have a very significant role in directing particles to cancer or other disease-associated cell types. Ultimately, we seek to explore and exploit these interactions to target layer-by-layer and layered complex nanoparticles to a range of different cell types. Efforts on the use of high throughput sampling of nanoparticle-cell interactions on understanding nanoparticle-cell interactions and targeted uptake will also be discussed.