Polymerization-induced self-assembly of N-substituted glycine N-carboxyanhydrides in selected solvents

Poly(sarcosine) (PSar)-based diblock copolypeptoid nanoparticles are promising alternatives to PEGylated polymeric nanocarriers. However, their preparation was limited by the slow polymerization kinetics and low assembly concentrations. Herein, we report the facile preparation of copolypeptoid nanoparticles through polymerization-induced self-assembly of N -substituted glycine N -carboxyanhydrides (NNCAs) in solvents with low polarity and weak hydrogen-bonding ability like dichloromethane (DCM). In contrast to the conventional polymerization in N , N -dimethylformamide (DMF), NNCAs were polymerized at an accelerated rate in DCM that minimized side reactions from water and other impurities. With isopentylamine-initiated PSar as the first stabilizing block, the polymerization of N -benzyl glycine N -carboxyanhydrides resulted in the formation of spherical or rod-like nano-assemblies at high solid contents (up to 15%) within several hours. We believe this work not only improves our basic understanding on NNCA polymerization behaviours, but also offers an efficient strategy to prepare drug nanocarriers with PSar corona, facilitating the downstream application studies.