Designed Conjugates for Targeted Therapies
The aim of this project area is to use polymer-peptide hybrid materials that show controlled assembly that can be used both as vehicles for delivery and models of protein aggregation. Both peptide and polymer components provide functionality to the materials, which are produced by a variety of controlled polymerization and “click” chemistry methods. Peptide-polymer conjugates, comprising peptides from structural proteins such as elastin and collagen, have demonstrated (triggered) assembly into nanoparticles and fibers. We anticipate great versatility in these approaches, as a wide variety of different polymer and peptide segments could potentially be employed to fine-tune the properties and functionality of the hybrid material.
During viral infections, in which many pathogens bind to the extracellular matrix (ECM), delivery from a scaffold promotes localized, sustained release and protection based on the interaction with the ECM. Our goal is to engineer delivery systems that similarly harness ECM interactions to induce high efficiency drug delivery vehicles. To this end, we are producing a variety of collagen-modified nanoparticles and demonstrating their interactions with ECM components for delivery.
Hydrogel Matrices in Regenerative Medicine
Elastomeric materials for regenerative medicine
Inspired by the outstanding mechanical properties of natural resilin, we have engineered a library of resilin-like polypeptides (RLP) for applications in regenerative medicine. Through the introduction of specific biomimetic amino acid sequences, the RLPs are endowed with proteolytic, cell binding and heparin sequestration properties that mimic the function of natural tissues. These RLPs can be cross-linked through small molecule cross-linkers, as well as PEG macromers, utilizing a variety of different chemistries. Our RLP hydrogels have been shown to be highly resilient and cyto-compatible. Currently, we are investigating these materials for vocal fold and cardiovascular applications.
Hydrogels that contain nanoparticles, composed of hydrophilic polymers that are lightly cross-linked, have a high degree of porosity that allows encapsulation of therapeutics and also high water content that contributes to biocompatibility. The dimensions of the nanoparticles within the hydrogels may be tuned to the appropriate size range for passive tumor targeting via enhanced permeability and retention (EPR) effect while their surfaces can be chemically modified with targeting moieties for active cellular targeting or with functional groups that are available for drug conjugation. In this project, we are producing both bulk PEG-based hydrogels and hydrogels that contain nanoparticles. These hydrogels are formed via thiol-maleimide Michael-type addition reactions and can be degraded in the presence of thiols owing to the reversibility of the specific chemical linkages employed. By taking advantage of the surface versatility of the hydrogel nanoparticles and the reversibility of engineered Michael-type adducts pioneered in our group, the materials represent very promising nanocarriers for targeted chemotherapies.