Abstract
Contact-electro-catalysis (CEC) has emerged as a promising strategy for reactive oxygen species (ROS) generation, primarily through water oxidation reactions (WOR) and oxygen reduction reactions (ORR), forming the foundation of contact-electro-dynamic therapy (CEDT). However, the high energy barrier of the ORR substantially limits the overall catalytic efficiency. Herein, we propose an alternative hydrogen peroxide (H(2)O(2)) reduction pathway to replace the ORR pathway, enabling the spontaneous generation of hydroxyl radicals (˙OH) without ultrasound assistance. Perfluorocarbon (PFC) nanoemulsions were prepared to construct a PFC-water liquid-liquid interface. Contact electrification at the PFC-water interface induces an interfacial electron-transfer process, wherein the PFC nanoemulsions act as mediators by capturing electrons from hydroxide ions (OH(-)) and subsequently transferring them to H(2)O(2), thereby generating ˙OH. Furthermore, ultrasound can enhance ˙OH production by increasing the frequency of liquid-liquid contact and facilitating electron release from negatively charged PFC (PFC*) to H(2)O(2). Importantly, we demonstrate that this H(2)O(2)-based CEC pathway represents a previously unrecognized mechanism underlying CEDT. In tumor microenvironments, where H(2)O(2) is overexpressed, this mechanism leads to enhanced ROS production and tumor cell death. This work uncovers a hidden catalytic route within the CEDT framework and provides new insights into the application of CEC for tumor therapy.