Triple-enzyme-mimicking AuPt3Cu hetero-structural alloy nanozymes towards cascade reactions in chemodynamic therapy

Oxidase-, peroxidase-, and catalase-like AuPt3Cu hetero-structural alloy nanozymes produced in a green and economic method induced cascade reactions to deplete glucose and glutathione and generate H2O2, O2, and reactive oxygen species in tumor microenvironment to cure cancer. [Display omitted] •Novel AuPt3Cu nanozymes with unique chemodynamic therapy performance are designed.•AuPt3Cu nanozymes mimic oxidase, peroxidase, and catalase efficiently.•AuPt3Cu cause cascade reactions to produce ROS in tumor cells and kill them.•IC50 to MCF-7 is 50 µg·mL−1, better than previously reported noble metal agents.•Tumor disappear on 14th day after treating AuPt3Cu without damage to normal organs. Inspired by unique enzyme-mimicking activities of Au and Pt nanocomposites and special roles of Cu components for native and artificial enzymes, we have designed the novel AuPt3Cu trimetallic hetero-structural nanozymes skillfully in this study. AuPt3Cu nanoparticles composed with Au-rich cores and Pt/Cu-rich outer shells with total size of 27.5 ± 3.1 nm are produced in aqueous solutions at 40 °C. Thanks to the alloyed Cu and special hetero structure, AuPt3Cu nanoparticles show excellent oxidase-, peroxidase-, and catalase-like activities. Catalyzed by AuPt3Cu, glucose and glutathione are oxidized by O2 (maximum reaction velocity, vmax, (5.65 ± 0.96) × 10-8, (9.82 ± 1.17) × 10-8 mol·L–1·s−1, respectively) and H2O2 is produced. Further, H2O2 is decomposed into O2 (vmax, 0.06 ± 0.003 mol·L–1·s−1) and reactive oxygen species (ROS, including ·OH, O2·–, 1O2). Then, O2 is decomposed into O2·– radicals. The catalytic reaction velocities of AuPt3Cu are higher than those of AuPt3 and PtCu0.4 counterparts. Because of the cascade reactions in tumor microenvironments, AuPt3Cu nanozymes own remarkable chemodynamic therapy (CDT) performance with IC50 of 50 µg·mL−1 towards cancerous MCF-7 cells. Starving and ROS therapy paths coexist. The tumors of mice bearing with MCF-7 disappeared completely on the 14th day after administering with 5 mg·kg−1 AuPt3Cu agents every 3 days. There are no damages to normal cells and organs, and liver and renal functions. Whether the synthetic strategy or CDT effects, AuPt3Cu nanozymes have unique advantages in cost, performance, and environmental conservation compared to noble metal-, transition metal oxide-, metal complex-, and polymer-relevant drugs.