Sonocatalytic In Situ Induced Oxygen Storm Precision Enhanced Reactive Oxygen Therapy for Pancreatic Cancer

Abstract Deep‐buried tissue, extremely hypoxic blood supply, and complex tumor microenvironment are considered to be the hardest difficult barriers to the accurate treatment of pancreatic cancer. Herein, a novel Au@Co₃O₄ (AC)‐polyvinylpyrrolidone (AC‐PVP) sonocatalytic agent and radiation sensitizer with a multicore–shell structure are synthesized by a mild reduction method for reshaping the special physiological environment of pancreatic cancer. Oxygen storms can be generated under ultrasonic activation by in situ catalyzed H₂O₂ in tumor tissue. The oxygen storm improves the ability to produce superoxide anions by sonodynamic therapy as well as rapidly supplements the oxygen‐dependent on active oxygen such as auger electrons produced by high‐energy ray ionization during radiotherapy (RT), further enhancing the efficiency of RT. Interestingly, AC‐PVP can reduce the intracellular glutathione (GSH) level, thus preventing the generated reactive oxygen species from being consumed by GSH. More importantly, the glucose oxidase‐like of AC‐PVP can catalyze glucose in tumor tissue to produce H₂O₂, and continuously provide substrates for sonocatalytic to form self‐cycling oxygen production. This study offers a novel paradigm for achieving in situ precise self‐oxygenation to overcome the special physiological barrier of pancreatic cancer and efficient sonodynamic synergistic radiotherapy.