Synthesis of Photo, Oxidative, and Reductive Triple-Stimuli-Responsive Block Copolymer Micelles as Nanocarriers for Controlled Release

With the rapid development of nanotechnology, stimuli-responsive nanomaterials have provided an alternative for designing controllable drug delivery systems due to their spatiotemporally controllable properties. The environment of the human body is complex and cancer cells proliferate rapidly; the traditional nanocarriers could not release the loaded drugs sufficiently, and the release level of the drug is not sufficient for the requirement of treatment. Herein, a photoresponsive, glutathione, and reactive oxygen species block copolymer mPEG_2k-ONB-SS-PO-mPEG_2k is prepared by Cu­(I)-catalyzed azide–alkyne cycloaddition click polymerization. The ο-nitrobenzyl groups, peroxalate ester bonds, disulfide bonds, and triazole units are regularly and repeatedly arranged in hydrophobic blocks. The photo, oxidative, and reductive responsive characteristics of the copolymers in different conditions were investigated by ultraviolet and visible spectrophotometry, dynamic light scattering, and transmission electron microscopy. Nile Red is encapsulated into the core of micelles as a model drug and exhibits the drug release behaviors in various environments. This research provides a way to design potential drug carriers and a promising platform for efficient intracellular drug delivery in cancer therapy.