ROPISA Synthetic Strategy for Photo-Crosslinked Aqueous Polypeptide Nano-Assemblies

Abstract

Polypeptides are emerging as an integral part of biomaterial research because of their unique ability to mimic natural protein-like secondary structures in water; however, they require a multistep self-assembly process to yield desired nano-sized objects for intended biomedical applications. In this study, we report a one-pot photo-crosslink strategy for stable polypeptide nanoparticle self-assembly by ring-opening polymerization-induced self-assembly (ROPISA) route. For this purpose, a cinnamoyl functionalized l-serine based N-carboxyanhydride (NCA) monomer is designed and subjected to ROPISA using PEG-amine as a hydrophilic macroinitiator in water which produced stable opalescent dispersions of amphiphilic PEG-polypeptide di-block copolymers having narrow molecular weights. Dynamic light scattering and HR-TEM analysis revealed the formation of spherical nanoparticles of 25–30 nm in size. The cinnamoyl anchored polypeptides underwent [2+2] cycloaddition under UV irradiation (265 nm) and the occurrence of the photo-crosslinking and its kinetics is studied by UV–visible spectroscopy. Notably, the nanoparticle size and structural integrity is remained unchanged and the particle morphology is found to be very stable. The core-cross-linked nanoparticles is found to be stable and behave as efficient scaffold for loading both water soluble and insoluble cargoes. This report opens an avenue to access photo-crosslinkable polypeptide nano-assemblies in the literature.