Poly(L -glutamic acid) grafted with oligo(2-(2-(2-methoxyethoxy)ethoxy) ethyl methacrylate): Thermal phase transition, secondary structure, and self-assembly

Thermoresponsive and pH-responsive graft copolymers, poly(L-glutamate)-g- oligo(2-(2-(2-methoxyethoxy)ethoxy)ethyl methacrylate) and poly(L-glutamic acid-co-(L-glutamate-g-oligo(2-(2-(2-methoxyethoxy)ethoxy)ethyl methacrylate))), were synthesized by ring-opening polymerization (ROP) of N-carboxyanhydride (NCA) monomers and subsequent atom transfer radical polymerization of 2-(2-(2-methoxyethoxy)ethoxy)ethyl methacrylate. The thermoresponsiveness of graft copolymers could be tuned by the molecular weight of oligo(2-(2-(2- methoxyethoxy)ethoxy)ethyl methacrylate) (OMEO₃MA), composition of poly(L-glutamic acid) (PLGA) backbone and pH of the aqueous solution. The α-helical contents of graft copolymers could be influenced by OMEO ₃MA length and pH of the aqueous solution. In addition, the graft copolymers exhibited tunable self-assembly behavior. The hydrodynamic radius (R_h) and critical micellization concentration values of micelles were relevant to the length of OMEO₃MA and the composition of biodegradable PLGA backbone. The R_h could also be adjusted by the temperature and pH values. Lastly, in vitro methyl thiazolyl tetrazolium (MTT) assay revealed that the graft copolymers were biocompatible to HeLa cells. Therefore, with good biocompatibility, well-defined secondary structure, and mono-, dual-responsiveness, these graft copolymers are promising stimuli-responsive materials for biomedical applications.