Harnessing hollow Prussian blue nanozymes for efficient photothermal lithotripsy while protecting the kidneys from oxidative stress injury

Kidney stones, given the high incidence and recurrence rates, pose a critical challenge to public health. High-power laser lithotripsy may induce damage to renal tissues, while existing therapeutic drugs have limitations in relieving the damage to renal tubular epithelial cells induced by oxidative stress. This injury promotes crystal aggregation and adhesion, further exacerbating cell damage and forming a vicious cycle. To address this problem, we proposed hollow Prussian blue (HPB) nanozymes for efficient photothermal lithotripsy while protecting the kidneys from oxidative stress injury. The in vitro lithotripsy results demonstrate that the efficiency of lithotripsy could be enhanced by adhering HPB to the surface of kidney stones thanks to its photothermal effect and stability characteristic under low power 808 nm near-infrared laser. No significant renal tissue damage was observed after the procedure, indicating its safety. In vitro HPB can simulate the activities of various antioxidant enzymes, thereby scavenge free radicals and protect cells from oxidative stress damage. Meanwhile, an animal model of renal CaOx crystals induced by glyoxylate was established to explore the safety and therapeutic effect of HPB. HPB could scavenge reactive oxygen species (ROS) and attenuate oxidative stress through its excellent biocompatibility and antioxidant enzyme activity, which protects renal tubular cells, upregulates the expression of antioxidant enzymes, downregulates proteins associated with stone adhesion and renal injury, and ultimately inhibits crystal deposition. Collectively, HPB not only provides an experimental theoretical foundation for novel lithotripsy techniques but also offers new insights into kidney protection and the prevention of crystal deposition.