W. N. Lacey Lectureship in Chemical Engineering
"Tuning stickiness and adapting charge of nanomaterials to target tissues and cell matrices" (Technical Lecture)
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 nanomaterials to specific tissues, as well as in adapting the transport of nanoparticles through typically charged and dense tissue matrices consisting largely of proteoglycans, polysaccharides or other biomolecular networks. In each case in which charge is an enabling factor for penetration in an oppositely charged matrix, 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. Systematic studies reveal a critical parameter space within which we must balance these properties while maintaining biocompatibility of the nanocarrier, and a means of defining the effective charge in such shielded systems. On the other hand, polyelectrolyte layered nanoparticles may be designed to exhibit adaptive charge that can enable modulated penetration and uptake of positively charged nanocarriers through the viscous barriers of bacteria biofilms which may enable delivery of drugs to resistant bacteria in a more targeted fashion.