Studies On Redox-Responsive Poly(Ether-Anhydride) Micelles For Cancer Therapy

Biodegradable polyanhydrides possess unique features like those that they can predominantly undergo surface erosion, and the payloads can be released by a steady speed. However, there is little work that has been published to describe the polyanhydride micelles with redox-responsiveness as a nanocarrier for drug delivery.In this study, we develop one type of new amphiphilic PEG-based ether-anhydride copolymer mPEG-ss-CPP-SA containing disulfide bonds between the hydrophilic and hydrophobic segments via classical meltcondensation polymerization. The copolymer can self-assemble into stable micelles with well-defined core-shell structure and a uniform size distribution with an average diameter of69nm. The glutathione-triggered disassembly behaviors of the micelles are evaluated from the changes of the micellar size and molecular weight.An approximate zero-order in vitro drug release mode with a fast speed can be achieved in a reducing and acid environment similar with that of tumor cells. In vitro cytotoxicity analysis demonstrate that the Cur-loaded redox-sensitive mPEG-ss-CPP-SA micelles are of great efficiency in inhibiting the growth of cancer cells due to the rapidly intracellular delivery of therapeutic agent and could effectively arrest HeLa cells in the G0/G1phase after24h incubation.The in vivo tumor inhibition e are evaluated by the analysis of changes of tumor volume, body weight and survival rate of tumor-bearing BABL/c mice receiving intravenous injection of different formulations and the histological analysis of tumor sections. Both the qualitative and quantitative results of the antitumor activity reveal that the redox-responsive micelles have a more significant therapeutic effect to artificial solid tumor compared to the redox-insensitive micelles.