Amphiphilic polypeptide-polyoxazoline graft copolymer conjugate with tunable thermoresponsiveness: Synthesis and self-assembly into various micellar structures in aqueous and nonaqueous media

Abstract

A “grafting onto” approach based on two different controlled ring-opening polymerization (ROP) techniques is developed to synthesize polytyrosine-graft-poly(2-ethyl-2-oxazoline) (PTyr-g-PEtOx) copolymer conjugates of varying main backbone and pendent chain lengths. This approach consists of syntheses of propargyl functionalized polytyrosine (PTyr-O-Pr) by ROP of tyrosine N-carboxyanhydride and azide functional poly(2-ethyl-2-oxazoline) (PEtOx-N3) by cationic ROP separately followed by their grafting using CuAAC reaction to afford the final graft copolymer conjugate (GCC). Owing to the presence of pendent hydrophiphilic PEtOx block, PTyr-g-PEtOx GCC exhibits LCST-type reversible phase transition behavior in water, which is tunable with respect to its concentration and the lengths of the main backbone and the pendent block. Again, the amphiphilic PTyr-g-PEtOx GCC molecules undergo self-assembly into spherical unit micelles and their consequent secondary aggregations into compound micelles both in aqueous and non-aqueous media. Upon increasing the solution temperature above LCST, micelles/compound micelles of PTyr-g-PEtOx GCC undergo further aggregation into higher order micellar agglomerates without any disruption of micellar structures as observed from DLS study. A hydrophobic dye (nile red) can easily be encapsulated into the hydrophobic PTyr core of the PTyr-g-PEtOx micelles in water, which remains stable without any release of the dye even when the temperature is increased above the LCST of the GCC.