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

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, v_max, (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 (v_max, 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 PtCu_0.4 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.