Polymeric micelles as drug delivery vehicles are popular owing to several advantages. In this study, a gemini amphiphile (gemini mPEG-Cys-PMT) consisting of hydrophilic poly(ethylene glycol) and hydrophobic poly(methionine) with cystine disulfide spacer was synthesized and its micellar properties for thiol- or reactive oxygen species (ROS)-dependent intracellular drug delivery were described. The cleavage of cystine linkage in a redox environment or the oxidation of methionine units in a ROS environment caused the destabilization of micelles. Such redox- or ROS-triggered micellar destabilization led to enhanced release of encapsulated doxorubicin (DOX) to induce cytotoxicity against cancer cells. Further, the therapeutic effects of the DOX-loaded micelles were demonstrated using the KB cell line. This study shows that thiol and ROS dual-responsive gemini micelles are promising platforms for nano-drug delivery in various cancer therapies.
