Reactive oxygen species (ROS) are one of the major intracellular metabolites.
Tumor cells are usually under oxidative stress and susceptible to further ROS insults due to the excessive increase in ROS levels. Moreover,
tumor cells also upregulate
antioxidant systems such as
glutathione (GSH) to counteract the damage caused by ROS. Therefore, the amplification of oxidative stress through increasing ROS levels to induce apoptosis could be a strategy for
tumor therapy. Here we report a redox-responsive
polymer micellar system, which is composed of
Pluronic F127-disulfide bond-d-α-tocopheryl
polyethylene glycol succinate (F127-SS-TPGS, FSST). The
micelles could be degraded by the cleavage of the
disulfide bond in the reductive intracellular environment, and release the ROS inducer,
TPGS, which induced cytotoxicity through elevating ROS levels and inhibited mitochondrial function in
tumor cells. These
micelles hardly affected the function of normal cells and showed good biocompatibility. The
paclitaxel-loaded FSST-PTX
micelles significantly improved the cytotoxicity of PTX. In vivo experiments revealed that the FSST-PTX
micelles prolonged the circulation and enhanced the treatment of PTX. In conclusion, FSST could be a potential vehicle for
cancer treatment.