Dr. Scott Medina
Assembled Peptide Biomaterials for Precision Medicine
Precision medicine represents a paradigm shift in the treatment of disease, where therapies can now be tailored based on a patient’s individual genetic and biomolecular profile. This approach has led to the discovery of new biomacromolecular therapeutics with high specificity and potency. However, these molecules are, in general, rapidly cleared from the systemic circulation and are incapable of entering cells to bind to intracellular targets, thus limiting their clinical viability. To overcome these challenges, our laboratory seeks to develop new peptide-based biomaterials, prepared via supramolecular assembly, that can localize and deliver biomacromolecules to cells with spatial and temporal control. In this talk, I will first summarize our efforts to develop cationic self-assembling peptide hydrogels that can encapsulate plasmid DNA, and enhance its immunostimulatory potential in vivo. Utilizing the structure-activity relationships identified in these studies, we have gone on to prepare de novo designed sequences that undergo templated assembly at the interface of an ultrasound-sensitive fluorous nanodroplet, forming a new class of peptide nanoparticles we term “nano-peptisomes”. As will be demonstrated, cell-impermeable biomolecular cargo present during nano-peptisome assembly can be encapsulated within the particle core, and subsequently delivered to the cytoplasm of cells following ultrasound-mediated carrier activation. Collectively, this work has begun develop new supramolecularly-assembled biomaterials with the potential to control cellular functions and augment immune responses, two important objectives towards realizing the full potential of precision medicine.