(3du) Drug Delivery with Control of Polymer Architecture and Chemical Composition: Combinatorial Synthesis of Diverse Nanoparticles for Intracellular Delivery

During my postdoctoral fellowship, we employed a modular design for the high-throughput study of >1,500 structurally distinct nanoparticles with cationic cores and variable shells, enabling elucidation of complexation, internalization, and delivery trends.  Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked with a diverse library of amines, followed by measurement of molecular weight, diameter, RNA complexation, cellular internalization, and in vitro siRNA and pDNA delivery.  Analysis revealed structure-function relationships and beneficial design guidelines, including a higher reactive block weight fraction, stoichiometric equivalence between epoxides and amines, and thin hydrophilic shells.  Cross-linkers optimally possessed tertiary dimethylamine or piperazine groups, and buffering capacity.  Covalent cholesterol attachment allowed for transfection in vivo to liver hepatocytes in mice.  The ability to tune the chemical nature of the core and shell may afford utility of these materials in additional applications.

Overall, my research involves studies at the Chemistry/Biology/Engineering/Nanoscience interface and strives to answer fundamental scientific questions and create innovative technologies and therapies that can benefit human health.  In particular, I believe that the development of future polymer therapeutics will require the ability to precisely control macromolecular architecture, order, and responsiveness.  My PhD research background in advanced synthetic polymer techniques, combined with my postdoctoral training in high-throughput methods, robotics, drug delivery, and animal studies will enable me to probe the effect of polymer architecture and chemical composition on the delivery of small molecule and biomacromolecular drugs.