Biodegradable thermal- and redox-responsive poly(l-glutamate) with Y-shaped oligo(ethylene glycol) side-chain and tunable phase transition temperature

Abstract

A series of poly(L-glutamate) bearing Y-shaped oligo(ethylene glycol)_x (OEG_x) side-chains (PPLG-g-EG_x, x = 2, 3 and 4) were synthesized via a combination of ring opening polymerization (ROP) of γ-propargyl-L-glutamate N-carboxyanhydride (PLG-NCA) with thiol–yne photoaddition. The solubility of the polypeptides in water was firstly investigated. PPLG-g-EG₃ and PPLG-g-EG₄ were soluble in water and displayed fully reversible thermal-responsive behaviors. Additionally, the polypeptides showed redox-responsive properties along with the conformation associated water solubility due to the presence of thioether groups in the side-chains. In particular, the clouding points (CPs) of the polypeptides are highly tunable depending on the degree of polymerization (DP), the side-chain length, the polymer/salt concentration, and the degree of oxidation/reduction. The key feature of our design is the simultaneous incorporation of thermal-responsive OEG units and redox-responsive thioether linkages by one-step thiol–yne photoaddition, which allows for precisely tuning the phase transition temperature by both stimuli. This synthetic approach offers a facile and efficient way to prepare polypeptide-based biomaterials with highly tunable properties.