Synthesis of polypeptide bearing 1,4-dithiane pendants for ROS-responsive drug release

Abstract Stimuli-responsive polypeptides have been intensively investigated for controlled drug release, owing to their favorable biocompatibility and biodegradability. In this work, we designed and synthesized a new kind of polypeptide bearing 1,4-dithiane pendants for reactive oxygen species (ROS)-responsive drug release. The polypeptide-based block copolymer was facilely synthesized by ring-opening polymerization (ROP) of 1,4-dithian-substituted L-glutamate N -carboxyanhydride (DTG-NCA) monomer using an amino-terminated poly(ethylene glycol) methyl ether (mPEG-NH 2 ) as the macromolecular initiator. The resultant block copolymer, mPEG- b -PDTG, could self-assemble into uniform micelles in aqueous medium owing to its amphiphilic structure. Then, the H 2 O 2 -triggered oxidation behaviors of the mPEG- b -PDTG micelles were studied by dynamic light scattering (DLS), FT-IR and turbidimetric assay. It was revealed that the oxidation of thioether into sulfoxide in the side chains would result in disassembly of the micelles. Furthermore, the ROS-responsive drug release behavior of the mPEG- b -PDTG micelles was verified by using Nile Red as a model drug. MTT assay also proved that mPEG- b -PDTG was non-toxic in B16F10 and L929 cells. Therefore, such a new class of oxidation-responsive polypeptide might provide a promising platform for ROS-responsive drug delivery.