Biomimetic copper single-atom nanozyme system for self-enhanced nanocatalytic tumor therapy

Single-atom nanozymes (SAZs) with peroxidase (POD)-like activity have good nanocatalytic tumor therapy (NCT) capabilities. However, insufficient hydrogen peroxide (H₂O₂) and hydrogen ions in the cells limit their therapeutic effects. Herein, to overcome these limitations, a biomimetic single-atom nanozyme system was developed for self-enhanced NCT. We used a previously described approach to produce platelet membrane vesicles. Using a high-temperature carbonization approach, copper SAZs with excellent POD-like activity were successfully synthesized. Finally, through physical extrusion, a proton pump inhibitor (PPI; pantoprazole sodium) and the SAZs were combined with platelet membrane vesicles to create PPS. Both in vivo and in vitro, PPS displayed good tumor-targeting and accumulation abilities. PPIs were able to simultaneously regulate the hydrogen ion, glutathione (GSH), and H₂O₂ content in tumor cells, significantly improve the catalytic ability of SAZs, and achieve self-enhanced NCT. Our in vivo studies showed that PPS had a tumor suppression rate of > 90%. PPS also limited the synthesis of GSH in cells at the source; thus, glutamine metabolism therapy and NCT were integrated into an innovative method, which provides a novel strategy for multimodal tumor therapy.