ChemBE Seminar Series: Thomas Epps III

Description

Thomas Epps III, a distinguished professor of chemical and biomolecular engineering, with a joint appointment in Materials Science & Engineering, at the University of Delaware, will give a talk titled "Responsive Polymer Nanoplexes — Linking In Vitro Experiments to In Vivo Outcomes" for the Department of Chemical and Biomolecular Engineering.

Epps is also director of the Center for Research in Soft Matter & Polymers; director of the Center for Hybrid, Active, and Responsive Materials, the new National Science Foundation Materials Research Science and Engineering Center at the University of Delaware; and deputy director of the Center for Plastics Innovation, the new Department of Energy Energy Frontier Research Center at the University of Delaware.

This is a hybrid event. To attend virtually, use Zoom ID 919 5918 2879 with passcode 270887.

Abstract:

Vascular bypass grafting is a routine treatment for cardiovascular diseases; however, nearly 50% of bypass grafts fail within a few years following surgery due to cellular inflammatory responses at the suture sites — a general concern for wound-healing applications. To overcome this problem, we synthesized novel diblock polymers to deliver nucleic acid therapeutics capable of promoting healing in a spatiotemporal manner. A key component of our design is a monomer containing photocleavable o-nitrobenzyl moieties linking cationic groups to the polymer backbone so that light irradiation can induce polymer hydrolysis and charge reversal. The polymers self-assemble with anionic nucleic acids in solution to form nanoparticle complexes with a PEG "stealth" coating. Application of a photo stimulus disrupts the electrostatic interactions to trigger the release of bound nucleic acids, such as siRNA, from the nanocomplexes. More significantly, our soft nanoparticles maintained stability in serum, exhibited robust cellular uptake, facilitated nanocarrier imaging, and were capable of photo-responsive on/off control over gene expression. These formulations enabled the knockdown of two key functional genes, IL1β and CDH11, that are implicated in inflammatory responses in human aortic adventitial fibroblasts. The complete knockdown of both genes, in combination, resulted in significant attenuation of TGF-β1- triggered fibroblast proliferation and differentiation into myofibroblasts, two of the primary hallmarks of fibrosis. Further attenuation over clinically relevant time scales was achieved by modulating the polyplex dosing regimen by taking input from a recently developed kinetic model, whose creation was enabled by our polymer design. Finally, we have very recently expanded our kinetic modeling to predict in vivo delivery results from in vitro experiments as confirmed via retrospective analyses, unlocking a potentially streamlined pathway to de novo design.