Reactive oxygen species (ROS) such as the superoxide anion radical (O2 ), hydrogen peroxide (H2O2), singlet oxygen CO2), and the hydroxyl radical (-OH) are produced in mammalian cells at low concentrations and act as signaling molecules. However, local overproduction of ROS in cells have been recently implicated in pathological conditions such as cancer.The increased level of ROS causes oxidative damage at the cellular level and plays a pivotal role in the progression of cancer. Design of ROS-sensitive materials to achieve site-specific delivery in vivo for release of therapeutics has therefore great potential. In this respect, polymeric micelles, formed from polymers composed of a water-soluble and hydrophobic segment are interesting as these can be used to encapsulate drugs. Since the hydrophobic segment is the driving force for micelle formation,making it become hydrophilic in response to ROS would lead to micelle dissociation and drug release. A well-known polymer with this hydrophobic to hydrophilic transformation is polypropylene sulfide that converts thioether groups into sulfoxides in response to ROS. Here, we report the design, synthesis, and characterization of doxorubicin (Dox)- loaded polymeric micelles with different thioether-motifs. Dissociation of these ROS-sensitive micelles in response to H2O2 was studied and the biological activity of the Dox-loaded micelles was evaluated in in vitro cell assays.