Biomimetic single-atom nanozyme system for efficient inhibition of gastric cancer ascites via SO2 gas-enhanced nanocatalytic cancer therapy

Abstract

Peritoneal metastasis is a frequent cause of death in gastric cancer, and it is newer mainly treated by hyperthermic intraperitoneal chemotherapy (HIPEC),whereas the patients experience serious side effects.Thus it is urgent to develop new alternatives, one example being Cu single-atom nanozymes (SAZ) with peroxidase (POD)-like activity and which have good nanocatalytic tumor therapy (NCT) capabilities. A previously described approach was used to produce platelet membrane vesicles (PV) and Cu SAZ. However, insufficient hydrogen peroxide (H2O2) limit NCT effects. Therefore, to overcome these limitations, through physical extrusion, an SO2 prodrug (benzothiazole sulfinate, BTS) and Cu SAZ were combined with PV to create PSB. BTS were able to release SO2 before inducing SO3− that can cause cell apoptosis. In addition, it can also down-regulate glutathione (GSH) while up-regulating H2O2 to significantly improve the catalytic ability of Cu SAZ. This study proved that PSB could suppress over 90% of the tumor while displaying good tumor-targeting abilities alongside great biocompability. Thus, by innovatively combining gas therapy with NCT, the system developed in this study not only provide a new strategy for addressing peritoneal metastasis of gastric cancer, but also offers useful insights into designing a new generation of cancer therapy for potential clinical applications.