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.