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

摘要

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-diox- aborolan-2-yl)benzyl acrylate], (PEG-b-P(PBA-co-PBEM), BCP for short) and alpha-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 H(2)O(2 )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.