Oxidation- and Temperature-Responsive Poly(hydroxyethyl acrylate-co-phenyl vinyl sulfide) Micelle as a Potential Anticancer Drug Carrier

Abstract

Poly(hydroxyethyl acrylate-co-phenyl vinyl sulfide) (P(HEA-co-PVS)), as an oxidizable amphiphilic polymer, was prepared for the fabrication of an oxidation- and temperature-responsive micelle for the delivery of doxorubicin (DOX). The interfacial activity of H2O2-treated P(HEA-co-PVS) was significantly lower than that of the untreated variety, possibly because of the oxidization of PVS. P(HEA-co-PVS) exhibited a lower critical solution temperature (LCST) behavior and the LCST increased upon H2O2 treatment. The copolymer micelles, prepared by the dialysis method, were found to be round particles (less than 100 nm) on TEM micrograph. The release degree of Nile red loaded in the micelles was higher when the H2O2 concentration was higher, possibly because the micelles could be solubilized more readily at a higher H2O2 concentration. The release degree was more strongly dependent on the oxidizing agent concentration when the temperature was higher. DOX loaded in the micelles suppressed the in vitro growth of KB cells (a human cancer cell type originating from the cervix) much more effectively than DOX loaded in an unoxidizable control micelle and free DOX, possibly because the copolymer would undergo an increase in its LCST, lose its amphiphilic property, and the micelles would be disassembled. The DOX-loaded micelles were readily internalized into KB cells, as evidenced by flow cytometry (FACS) and confocal laser scanning microscopy (CLSM).