Join us to hear from Dr. Joel Schneider, the Deputy Director of the Center for Cancer Research!

Abstract: Self-assembling peptides have proven useful as building blocks for the construction of materials. We designed a class of peptide hydrogels that allows for the direct encapsulation of therapeutics and their subsequent local delivery to tissue. Peptide assembly leading to gels can be triggered in the presence of small molecules, proteins, nucleic acids, cells, and nanoparticles resulting in their direct encapsulation. Resultant gels display shear-thin/recovery mechanical properties, allowing their direct application to targeted tissue by syringe or spray, where they deliver their payload locally. A deep mechanistic and structural understanding of our materials has allowed the development of gels that facilitate a broad range of applications including microanastomosis, gels that limit tissue rejection after transplantation, and gels as treatments for mesothelioma, a hard-to-treat cancer. Another approach for designing materials is inspired by how many drugs bind their biological targets, which is selectively and reversibly with characteristic binding constants and on/off-rates. These same targets can serve as depots for drug loading, and be used as building blocks for the construction of drug delivery materials. For example, self-assembling a given biological target should afford a material with a tunable copy number of selective binding sites that can house and subsequently release drug at predictable rates. We demonstrate feasibility of this approach by preparing gel networks by self-assembling amphiphiles containing the drug target of the antibiotic vancomycin. This drug kills bacteria by reversibly binding to the dAla-dAla dipeptide found within bacteria, inhibiting cell wall biosynthesis. Gel networks formed by dAla-dAla assembly serve as selective depots for vancomycin and provide sustained release of drug over months in vivo. Biophysical experiments and release simulations using mathematical models of mass transport dynamics indicate that drug release is largely dependent on the on/off-rates defining the reversible binding event between drug and target. Lastly, we demonstrate that the gel can be reloaded multiple times by simple tail-vein injection after releasing its cargo.

Bio: Dr. Schneider received a Ph.D. in Organic Chemistry from Texas A&M University with Jeffery Kelly and then a postdoc with William DeGrado at the University of Pennsylvania School of Medicine studying protein design. After which, he joined the faculty at the University of Delaware (UD). As Professor of Chemistry and Biochemistry at UD, he was recruited in 2010 to the National Cancer Institute (NCI), National Institutes of Health to serve as Chief of the newly established Chemical Biology Laboratory, where he developed an internationally recognized Department. In his independent research, Dr. Schneider is developing novel materials for use in the local delivery of therapeutics. His work has produced over 120 publications, multiple patents and over 250 invited lectures. He also serves as scientific mentor to young scientists, having trained a cadre of Ph.D. students, postdoctoral fellows, post baccalaureate fellows and high-school students who have taken excellent positions in both industry and academia. Dr. Schneider also serves as Deputy Director of the Center for Cancer Research, NCI as well as the past president of the American Peptide Society.