Enhancing trigger sensitivity of nanocarriers through organocatalytic oxidant activation

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The redox balance in tumor and diseased cells often leads to the production of reactive oxygen species (ROS). Many ROS-responsive materials based on sulfur oxidation have been reported with the goal of achieving controlled delivery at the tumor. However, these materials often lack responsiveness to low ROS concentrations present in the tumor environment. To address this, we use organocatalysis to achieve an enhanced response of thioether-based nanocarriers triggered by low concentrations of ROS. Using block copolymer micelles that can disassemble through thioether oxidation followed by ester hydrolysis, this work shows how an in-situ-formed imine oxidation catalyst can enhance disassembly kinetics at low millimolar hydrogen peroxide concentrations. The results show that with organocatalysis, Nile Red-loaded micelles release their cargo twice as fast compared to uncatalyzed conditions. This study highlights the potential of organocatalysis as a valuable strategy to enhance the responsiveness of biomarker-triggered delivery systems.