Facile Preparation of Crosslinked PEG-Polypeptide Drug Nanocarriers Through Biphasic Polymerization of Crude N-Carboxyanhydrides

Poly(ethylene glycol) (PEG)-polypeptide drug nanocarriers have garnered increasing attention during last decades. However, the tedious polymer synthesis and the stability issue greatly limit their further development. Herein the biphasic polymerization platform is reported for the easy access of a series of crosslinked PEG-polypeptide nanoparticles for enhanced drug loading and selective drug release. The accelerated polymerization allows for the preparation of a library of PEG-polypeptides from crude monomers with different polypeptide segments for structural optimization. Nanocarriers with redox-responsive de-crosslinking and enhanced drug loading are therefore obtained based on the model drug, doxorubicin, which exhibits selective killing of cancer cells. This study provides a synthetic method for efficient preparation of PEG-polypeptide nanocarriers, benefiting the downstream drug loading and therapeutic studies.