Maximizing Peptide Therapeutic Delivery Through Biomodulatory Materials Design

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

Project Summary As the biomedical community tackles grand challenges like site-specific pharmaceutical delivery and organ regeneration, strategies employing simple products serving a singular function are suboptimal. Instead, novel, multi-dimensional strategies need to be developed to achieve the next breakthroughs especially in fields like immunoengineering and regenerative medicine. Nowhere is this effort more necessary than in the use of bioactive peptides where considerable hurdles exist in achieving spatiotemporal control over their delivery. While a wide range of biomaterials have been employed to attempt to achieve this goal, they have been mostly non- bioactive in nature minimizing their maximum drug loading and device fabrication potential while often leading to limited higher order structure of associated peptides. To address this issue, the long-term goal of the Ulery Laboratory is to engineer the physicochemical properties of biomaterials to allow them to directly modulate cell and tissue responses. These novel biomaterials, defined as biomodulatory materials, are being utilized individually or in combination with other bioactive factors to produce desirable biomedical outcomes. Our recent progress in this research space has focused on leveraging peptide amphiphile micelles to create complex nanoparticles and hydrogels. By generating novel biomaterials from bioactive peptides, we have been able to create self-adjuvanting vaccines, anti-inflammatory therapeutics, cell-targeted cancer therapies, and bone regenerating products. While exciting in its own right, we have been able to achieve these results with peptides that do not have the peptide chemistry that lends to their stabilization through other means like stapling and cyclization. In this Maximizing Investigators’ Research Award, we will build on our previous efforts to engineer peptide-based biomodulatory materials that can serve as translational platform technologies for a variety of biomedical applications. First, we will use a combination of computational and experimental techniques to generate design rules for micellar nanoarchitectures to allow for the rapid production of micellar systems from new bioactive peptides. In addition to nanoparticle shape, we will characterize the influence that other physical properties such as charge, stability, and product entrapment have on peptide amphiphile micelle function. Finally, we will focus on programming multiple cell recruitment and differentiation outcomes into hydrogel systems to achieve coordinated complex bioactivity. These efforts are well suited as a foundation to continue to build our laboratory’s research program upon including progressing into the new application areas such as treatments for autoimmune diseases, tumors, and neural disorders.