Ultrasound-mediated Cu2+/Cu+ redox cycling activates peroxymonosulfate for oxygen-independent reactive X species (X = O/S) therapy

Reactive oxygen species (ROS) can induce oxidative damage to biomolecules within tumor cells, making them suitable for tumor therapy. However, the effectiveness of these ROS in treating tumor cells is restricted due to their short half-life or short diffusion distance. Sulfate radicals (SO4•–), with a longer half-life and higher oxidation potential, provide a compelling alternative. Herein, we propose an efficient strategy to activate peroxymonosulfate (PMS) and produce SO4•– and •OH by using ultrasound-mediated Cu2+/Cu+ redox cycling, enabling oxygen-independent synergistic tumor therapy. Notably, this redox cycle ensures the continuity of effective Cu+ catalytic sites and prevents adverse effects on healthy tissues. The density functional theory results demonstrate that the decisive copper valence-conversion step is derived from the ultrasound-induced excitations of electrons in spin-down bands of Cu2(OH)PO4. This ultrasound-controlled transition metal valence alteration enables in-situ activation of a nontoxic drug to produce toxic reactive X (X = O/S) species in an O2-independent manner, offering an efficient, adaptable and universal methodology for treating hypoxic tumors in living systems.