An "AND" Logic Gate S-Scheme Nanozyme for Magneto-Pyroelectric Dynamic Therapy Integrated With Lactate-Urate Immunometabolic Remodeling in Glioblastoma.

Glioblastoma (GBM) therapy remains limited by poor blood-brain barrier (BBB) penetration and an adaptive, immunosuppressive tumor microenvironment (TME). Here, we engineer multifunctional FeWOx@Ag/Bi2Te3-HA nanozymes (FABH) to integrate magneto-pyroelectric dynamic therapy (MPEDT), metabolic regulation, immune activation, and near-infrared II fluorescence imaging. Under alternating magnetic field (AMF) stimulation, the Ag/Bi2Te3-FeWOx S-scheme heterojunction promotes pyroelectric charge separation and reactive oxygen species (ROS) generation, thereby strengthening MPEDT and inducing immunogenic cell death. FABH nanozymes also show AMF-enhanced L-cysteine oxidase (LCO), reduced nicotinamide adenine dinucleotide (NADH) oxidase (NOX), lactate oxidase (LOX), and xanthine oxidoreductase (XOR) activities. These cascaded activities deplete glutathione, improve oxygen availability, block protective autophagy, and remodel lactate- and urate-associated metabolism to activate innate and adaptive antitumor immunity. Magnetic guidance further enables FABH nanozymes to cross the BBB and accumulate in deep GBM lesions, while silver ion incorporation improves thermoelectric performance and supports real-time NIR-II imaging. This integrated strategy promotes GBM ablation through BBB penetration, ROS storm generation, autophagy blockade, and immunometabolic remodeling.