Fine structural tuning of the assembly of elastin–collagen peptide conjugates with drug loading and manipulation of molecular interactions

Abstract

Elastin–collagen nanoparticles (ECnPs) have been shown in our previous studies to self-assemble into different morphologies, including nanoplates and nanovesicles, by manipulating the sequence length of the elastin-like peptide (ELPs) and collagen-like peptide (CLPs) of a given conjugate. In this work, we demonstrate that the morphologies of ECnPs can also be modulated, for a given ECnP sequence, with variations in solution pH and/or the amount of encapsulated drug. Specifically, the peptide (VPGYG)₆-(GPO)₈ preferentially formed nanovesicles under basic conditions but assembled into nanoplates under acidic conditions. Another sequence, (VPGWG)₂(VPGFG)₂-(GPO)₈, produced nanovesicles when loaded with a high concentration of dexamethasone-carboxyfluorescein (Dex-CF), but transitioned to nanoplates at lower drug loading. Furthermore, in addition to the different morphologies observed for a given set of initial solution conditions, our studies also illustrate the possibility of triggering vesicle-to-plate transformations for a given ECnP with release of Dex-CF over time. These results highlight multiple avenues for controlling ECnP morphology, expanding their applicability as a flexible and efficient drug delivery platform.