Nanocatalysts‐Augmented and Photothermal‐Enhanced Tumor‐Specific Sequential Nanocatalytic Therapy in Both NIR‐I and NIR‐II Biowindows

The tumor microenvironment (TME) has been increasingly recognized as a crucial contributor to tumorigenesis. Based on the unique TME for achieving tumor-specific therapy, here a novel concept of photothermal-enhanced sequential nanocatalytic therapy in both NIR-I and NIR-II biowindows is proposed, which innovatively changes the condition of nanocatalytic Fenton reaction for production of highly efficient hydroxyl radicals (•OH) and consequently suppressing the tumor growth. Evidence suggests that glucose plays a vital role in powering cancer progression. Encouraged by the oxidation of glucose to gluconic acid and H₂ O₂ by glucose oxidase (GOD), an Fe₃ O₄ /GOD-functionalized polypyrrole (PPy)-based composite nanocatalyst is constructed to achieve diagnostic imaging-guided, photothermal-enhanced, and TME-specific sequential nanocatalytic tumor therapy. The consumption of intratumoral glucose by GOD leads to the in situ elevation of the H₂ O₂ level, and the integrated Fe₃ O₄ component then catalyzes H₂ O₂ into highly toxic •OH to efficiently induce cancer-cell death. Importantly, the high photothermal-conversion efficiency (66.4% in NIR-II biowindow) of the PPy component elevates the local tumor temperature in both NIR-I and NIR-II biowindows to substaintially accelerate and improve the nanocatalytic disproportionation degree of H₂ O₂ for enhancing the nanocatalytic-therapeutic efficacy, which successfully achieves a remarkable synergistic anticancer outcome with minimal side effects.