Sonodynamic remedy (SDT) is gaining recognition in most cancers remedy on account of its superior controllability and excessive tissue permeability. Nonetheless, the efficacy of SDT is severely diminished by the transient era of restricted reactive oxygen species (ROS). Herein, we introduce an acid-activated nanosonosensitizer, CaO2@PCN, by the controllable coating of porphyrinic metal-organic frameworks (PCN-224) on CaO2 to induce cascaded oxidative stress in tumors. The PCN-224 doping might generate ROS throughout SDT to induce intracellular oxidative stress and irregular calcium channels. In the meantime, the ultrasound additionally promotes extracellular calcium inflow. As well as, the CaO2@PCN will sequentially degrade within the tumor cell lysosomes, releasing Ca2+ and H2O2 to induce additional irregular calcium channels and elevate the degrees of Ca2+. Inadequate catalase (CAT) in tumor cells promotes intracellular calcium overload, which might induce persistent ROS era and mitochondrial dysfunction by way of ion interference remedy (IIT). Extra importantly, PCN-224 additionally protects CaO2 towards vital degradation below impartial circumstances. Therefore, the well-designed CaO2@PCN produces synergistic SDT/IIT results and protracted ROS towards most cancers. Extra notably, the acidity-responsive biodegradability endows CaO2@PCN with glorious biosafety and promising medical potential.
