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.