Construction of glucose and H₂O₂ dual stimuli-responsive polymeric vesicles and their application in controlled drug delivery

Herein, glucose and H₂O₂ stimuli-responsive vesicles are constructed based on host–guest interaction between a diblock copolymer, poly(ethylene glycol)-b-poly[3-acrylamidophenylboronic acid-co-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate], (PEG-b-P(PBA-co-PBEM), BCP for short) and α-cyclodextrin. In the presence of glucose, the vesicles are transformed to giant swollen spherical micelles because of the formation of a negatively charged tetravalent form between phenylboronic acid and glucose. On the other hand, the vesicles are totally disassembled when they are exposed to H₂O₂, which is due to the H₂O₂-mediated degradation of the pendant phenylboronic acid pinacol ester. The glucose and H₂O₂ stimuli-responsive vesicles are then applied in the controlled release of water-soluble anticancer drug, doxorubicin hydrochloride (DOX). Upon external stimuli, the DOX displays a faster release rate than that without stimuli. Moreover, the polymeric vesicles show an excellent cytocompatibility toward MCF-7 cells, and the drug-loaded vesicles exhibit a lower cytotoxicity than free drug toward cancer cells. The drug-loaded vesicles can be taken up by MCF-7 cells and further release the DOX in cancer cells due to the high glucose and H₂O₂ concentration in tumor cells, while they have negligible effect on normal cells, which may be important for applications in the therapy of cancers as a controlled-release drug carrier.