One-pot preparation of polypeptide nanogels in aqueous solution via ring-opening polymerization-induced nano-gelation

Abstract

Polypeptide-based nanogels possess excellent biocompatibility, stability, and biological functions for many applications. Herein, we present one-pot synthesis of polypeptide nanogels by an innovative strategy of ring-opening polymerization induced nano-gelation of L-cystine N-carboxyanhydride (CYS-NCA) and γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) using α-amino-poly(ethylene oxide) (mPEG-NH₂) as a macroinitiator in an aqueous solution. The polymerization kinetics was systematically investigated by FTIR and ¹H NMR. We demonstrated the formation of the core cross-linked nanogels with disulfide linkages, which are extremely stable over a wide range of 1 mg mL⁻¹–0.001 mg mL⁻¹. Furthermore, the redox sensitivity of the nanogels allows for smooth loading and in vitro release of indomethacin. Thiol–ene chemistry was demonstrated to be an efficient method for the modification of the nanogels after reductive reactions. The robust and effective method combined with the excellent biodegradability of the polypeptides offers great potential for the preparation of new-generation functional nanomaterials.