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.