A Needle-Like H2S-Releasing and H2O2 Self-Replenishing Nanoplatform for Enhanced Chemodynamic Tumor Immunotherapy.

The tumor microenvironment (TME) significantly restricts chemodynamic therapy (CDT) efficacy through hypoxia and antioxidant defenses. An intelligent cascade nanosystem, PTA-SnS2@GOx, is developed by integrating a tannic acid-modified Prussian blue analogue core, SnS2 shell, and glucose oxidase (GOx) activation module. The needle-like nanostructure enhanced tumor accumulation and cellular uptake. GOx-mediated glucose oxidation generated H2O2 and gluconic acid, triggering pH-responsive H2S release from SnS2. This gas disrupted mitochondrial respiration and catalase activity, alleviating hypoxia while elevating intracellular H2O2 levels. The oxygenated TME subsequently amplified GOx biocatalysis, establishing a self-sustaining cycle of H2O2 production and acidification. Concurrently, Sn4+ ions depleted glutathione, synergistically enhancing Fenton-like reactions in the PTA core for reinforced ROS generation. This multi-tiered strategy achieved effective CDT through the coordinated mechanisms: continuous H2O2 self-supply, pH reduction, and redox homeostasis disruption. Notably, the nanosystem induced immunogenic cell death, promoting dendritic cell maturation and repolarizing tumor-associated macrophages from M2 to M1 phenotype, thereby remodeling immunosuppressive TME and activating systemic antitumor immunity. The synergistic integration of self-amplifying CDT with immune sensitization demonstrates superior tumor suppression in vivo. This study provided an intelligent paradigm for cancer theranostics by combining self-supplying H2S/H2O2-enhanced CDT with sensitized immunotherapy.