The feasibility of ROS- and GSH-responsive micelles for treating tumor-initiating and metastatic cancer stem cells

Currently, research on cancer therapy is focused on cancer stem cell therapy to overcome drug resistance and tumor recurrence. Although most studies thereof have focused on the effects of functional nanocarriers on cancer therapy, there is little discussion on the effect of nanocarriers on tumor-initiating cancer stem cells (TICSCs) and metastatic cancer stem cells (MCSCs). Therefore, a glutathione (GSH)-responsive micelle, a reactive oxygen species (ROS)-responsive micelle, and a dual GSH-/ROS-responsive micelle were prepared to evaluate the feasibility of using stimuli-responsive micelles to treat TICSCs and MCSCs. The experimental results demonstrate that ROS-responsive and dual ROS-/GSH-responsive micelles efficiently induce the death of both TICSCs and MCSCs because they could release drugs on both CSCs. However, GSH-responsive micelles were sensitive to TICSCs but not to MCSCs because the latter expressed a low GSH level. Relevant results suggest that the micelles with an ROS-responsive characteristic have great potential for delivering payloads efficiently to treat both TICSCs and MCSCs.