Bimetallic multi-enzyme nanozyme with spatiotemporal-regulated dual-gas release for enhancing catalytic/gas therapy

The reactive oxygen species (ROS) mediated catalytic therapy is severely hindered by the insufficient endogenous substrates, and gas therapy is an emerging therapeutic method, which can improve ROS-mediated antitumor efficacy through modulating oxidative stress. In this study, by coating periodic mesoporous organosilica (PMO), loading sodium nitroprusside (SNP) and depositing ultrasmall Au nanoparticles (AuNPs) on the surface of platinum‑palladium (PtPd), we reported a multi-enzyme nanozyme (PtPd@PMO@SNP@Au) to enhance catalytic/gas therapy through producing ROS storm and spatiotemporally regulating dual-gas release. The PtPd@PMO@SNP@Au nanozyme exhibited the multi-enzyme-like activities of glucose oxidase, catalase, peroxidase, and oxidase, in which the cascade reactions significantly triggered the ROS storm. Moreover, the PtPd@PMO@SNP@Au nanozyme possessed the glutathione (GSH) depletion and near-infrared II photothermal performances, by which the GSH-responsive hydrogen sulfide (H 2 S) and photothermal-responsive nitric oxide (NO) release were achieved. By combining the ROS storm generation and spatiotemporal-regulated NO/H 2 S release, the developed PtPd@PMO@SNP@Au nanozyme greatly induced the cell apoptosis, and enhanced the catalytic/gas therapy of tumors.