Hydroxyl radical generation from H 2 O 2 via liquid–liquid contact-electro-catalysis

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 (H₂O₂) 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 H₂O₂, 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 H₂O₂. Importantly, we demonstrate that this H₂O₂-based CEC pathway represents a previously unrecognized mechanism underlying CEDT. In tumor microenvironments, where H₂O₂ 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.