Morpho-crystallo-electronic Co-optimization of PtAu/GOx nanozyme for enhanced NIR-II photothermal-cascade catalytic...

Cascade catalytic therapy offers a specific strategy by sequentially converting highly expressed endogenous substances (e.g., H₂O₂, glucose) in the tumor microenvironment into highly cytotoxic reactive oxygen species to kill cancer cells. Photothermal therapy has high precision and low side effects. The combination of photothermal therapy and cascade catalytic therapy holds promise in overcoming current limitations in tumor therapy. Although noble metal-based nanozymes exhibit both stable photothermal conversion and multiple catalytic activities, their intrinsic inefficiency and unclear structure-activity relationships hinder further clinical translation. This work proposed a "morphological-crystallographic-electronic" tripartite synergistic optimization strategy. A multifunctional PtAu/GOx composite nanozyme was synthesized through wet-chemical methods, leveraging high surface area for active site exposure, high/low-index hybrid facets for optimized substrate adsorption, and Au-Pt charge transfer to regulate d-band centers for enhancing the multi-enzyme-like catalytic activities. This enables an efficient cascade catalytic cycle (H₂O₂→O₂→more H₂O₂→•OH) within tumor. Moreover, the PtAu/GOx composite nanozyme has superior photothermal conversion performance under the irradiation of second near-infrared laser and can synergistically achieve the photothermal-augmented tumor cascade catalytic therapy. Advanced characterizations and simulations were employed to decipher their structure-activity relationships. Both in vitro and in vivo experiments validate the enhanced antitumor efficacy of the PtAu/GOx nanozyme through the synergistic optimization.