Abstract
The reactive oxygen species (ROS) responsive amphiphilic poly(ethylene glycol)-b-poly(thioketal) (mPEG-b-PTK) copolymer was synthesized by enzyme-catalyzed polymerization for the first time. Core crosslinked (CCL) micelles were prepared via thiol-ene click reaction between the double bond of the side chain of mPEG-b-PTK and the thiol group of pentaerythritol tetrakis (3-mercaptopropionate) as a crosslinker under UV light. The success of crosslinking was verified by NMR and IR. CCL micelles showed better stability in stability against dilution and storage stability experiments compared with the uncrosslinked (UCL) micelles. The ROS-responsiveness of CCL micelles was characterized by DLS, TEM, NMR, AFM and SEM. In vitro release studies, CCL micelles encapsulating doxorubicin (DOX) showed a faster release rate of nearly 100% within 32 h in PBS containing 5 mM H2O2 compared to the control without H2O2. Cytotoxicity test demonstrated good biocompatibility of CCL micelles and low toxicity with cell viability above 82% and 86% in HeLa cells and HUVEC cells, respectively. And CCL DOX-loaded micelles exhibited great anticancer activity with IC50 value about 4.8 mg/L for Hela cells. Finally, flow cytometry and confocal laser scanning microscope (CLSM) showed that DOX-loaded micelles had excellent internalization efficiency in HeLa cells. The obtained ROS-responsive CCL micelles held promise for anticancer drug delivery.
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