One-step synthesis of PtRhMo/Rh nanozymes for mitochondrial damage-mediated photothermal/enzymatic therapy
Photothermal therapy (PTT) is limited by heat shock protein (HSP) upregulation and mitochondrial-encoded thermoresistance in tumor cells. This study reports PtRhMo/Rh multi-metal nanozymes synthesized via a one-step method for cascade enzymatic therapy and enhanced PTT. The nanozymes exhibit a photothermal conversion efficiency of 55.6% and multiple enzyme-like activities: catalase (CAT), oxidase (OXD), peroxidase (POD), glutathione peroxidase (GPx), and NADH oxidase (NOX). These activities generate reactive oxygen species (ROS) and deplete NADH, disrupting the electron transport chain (ETC) and causing mitochondrial damage. This downregulates HSP70, sensitizing tumors to heat. In vivo biocompatibility tests at 400 ppm showed no hemolysis and no significant pathological changes in major organs. Hematological parameters remained stable. The synergistic approach directly kills tumor cells and weakens thermoresistance, offering a promising strategy for clinical translation.