Synthesis and Thermoresponsive Properties of Biocompatible and Biodegradable Triblock Copolymers Bearing Linear or Y-Shaped OEG Pendants

Biocompatible and biodegradable thermoresponsive polymers are of great interest in smart biomedical applications. Herein, triblock copolymers (6a and 6b) comprised of hydrophobic poly(propylene glycol) (PPG) and OEGylated polypeptides bearing Y-shaped or linear pendants are prepared by ring-opening polymerization of reactive N-carboxyanhydride monomers and subsequent side chain modification of polypeptides. OEGylated triblock copolymer bearing Y-shaped (6a) or linear pendants (6b) with similar main chain length and the same amount of oligo(ethylene glycol) (OEG) units are successfully prepared as verified by H-1 NMR, FTIR, and GPC. CD analysis reveals that 6a with Y-shaped OEG pendants shows thermal- or salt-induced destabilization of alpha-helical conformation in water. Both 6a and 6b show reversible lower critical solution temperature (LCST)-type phase transitions in DI H2O or PBS. Incorporation of a PPG segment leads to a significant decrease of the LCST-type cloud point temperature (T-cp). Consequently, 6a and 6b show T-cp to human body temperature at low polymer concentrations (<= 0.5 mg mL(-1) in PBS). Moreover, 6a and 6b show low in vitro cytotoxicity and biodegradability in the presence of proteinase K. The results indicate that the thermoresponsive properties of LCST-type polymers can be readily tuned by constructing Y-shaped pendants as well as incorporation of hydrophobic polymer building blocks.