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

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.