Azoreductase-triggered fluorescent nanoprobe synthesized by RAFT-mediated polymerization-induced self-assembly for drug release

Abstract

Azobenzene-based polymeric nanoparticles have emerged as promising candidate for biological detection and controlled drug release in an anaerobic environment for colon disease treatment. Herein, we report a novel and efficient polymerization-induced self-assembly (PISA) strategy for fabricating polymeric nanovehicles to load drugs for triggered release and fluorescence detection based on a TPE (tetraphenylethylene)-azobenzene fluorescence probe sensitive to hypoxic microenvironments. In this study, a series of PISA-nanoparticles, including micelles and vesicles, were synthesized by reversible addition–fragmentation transfer (RAFT) dispersion copolymerization of monomers butyl methacrylate (BMA) and reductive-responsive TPE-AZO-MA (TPE-azobenzene derived methacrylate) in a 1,4-dioxane/water mixture. Subsequently, polymeric micelles loaded with doxorubicin (DOX) in situ were successfully obtained by PISA. Furthermore, the release and fluorescence change of PISA-formed micelles loaded with DOX were studied in a simulated colon environment under the action of azoreductase. As expected, the drug-loaded micelles showed an effective DOX release during enzyme hydrolysis within 24 h owing to azo bond cleavage. Meanwhile, significant fluorescence enhancement was observed, accompanied by the release process. This was due to the aggregation-induced emission (AIE) performance of TPE being efficiently activated by elimination of the fluorescence resonance energy transfer (FRET) process, also owing to azo bond cleavage. Finally, the cytotoxicity and cellular uptake of the blank micelles and DOX-loaded micelles in vitro were evaluated.