Development and characterization of extracellular matrix inspired peptides for nanoparticle self-assembly

Date
2017
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
The extracellular matrix (ECM) is a dense mesh-like network of proteins, proteoglycans, and glycoproteins that imparts physical stability to tissues and plays key roles in cell signaling and behavior such as cell adhesion, proliferation, differentiation, and survival. Physiochemical irregularities or disruptions to certain components of the ECM, such as collagen, can lead to diseases like osteogenesis imperfecta, and osteoarthritis. Current systemic delivery approaches to treat such diseases suffer from off-target effects, suggesting a significant need for ECM targeted therapeutics. ☐ In the last decade ECM inspired polypeptide materials, including elastin like peptides (ELPs) and collagen-like peptides (CLPs), have garnered significant interest in the field of drug delivery. This is owed to the general biocompatibility and thermoresponsivity of both peptides, but also the ability of CLP to target and hybridize to denatured collagen protein in the body. Recently, our group has reported on the assembly of thermoresponsive elastin-b-collagen like peptide nanovesicles that are capable of dissociating at high temperature (70°C). In an effort to modify this temperature of dissociation, and in turn the temperature of CLP-collagen hybridization, a small library of CLP sequences was synthesized. The propensity of four different CLP sequences to form triple helices was measured using circular dichroism wavelength scans and the melting temperatures for each were determined. Characterization of the inverse transition temperature of two different ELP sequences was also completed through light scattering experiments to ensure its role in nanoparticle formation. ☐ Lastly the conjugation of a particular ELP to a small selection of CLPs was performed and characterized for their ability to form nanoparticles. The melting temperature and repeat length of the CLP domain was found to be of critical importance to nanoparticle formation, with one CLP forming particles, while the same CLP with a single repeat unit shorter was not. The ability of these two conjugate systems to form nanoparticles was correlated with their overall triple helical stability and melting temperature. Additionally, the conjugate that was shown to form particles was found to possess characteristics that were more idealized for drug delivery than the previous system. Future work will be focused on determining if the effect of the nanoparticle formation and lower critical solution temperature properties of the particle is a result of CLP triple helical melting temperature or simply an artefact of assembly of a particle with a smaller hydrophilic volume fraction.
Description
Keywords
Applied sciences, Collagen, Hybridization, Nanoparticle, Peptide, Thermoresponsive
Citation