Advances in nanotechnology have enabled the rapid development of stimuli-responsive therapeutic nanomaterials for precision gas therapy. Hydrogen sulfide (H 2 S) is a significant gaseous signaling molecule with intrinsic biochemical properties, which exerts its various physiological effects under both normal and pathological conditions. Various nanomaterials with H 2 S-responsive properties, as new-generation therapeutic agents, are explored to guide therapeutic behaviors in biological milieu. The cross disciplinary of H 2 S is an emerging scientific hotspot that studies the chemical properties, biological mechanisms, and therapeutic effects of H 2 S. This review summarizes the state-of-art research on H 2 S-related nanomedicines. In particular, recent advances in H 2 S therapeutics for cancer, such as H 2 S-mediated gas therapy and H 2 S-related synergistic therapies (combined with chemotherapy, photodynamic therapy, photothermal therapy, and chemodynamic therapy) are highlighted. Versatile imaging techniques for real-time monitoring H 2 S during biological diagnosis are reviewed. Finally, the biosafety issues, current challenges, and potential possibilities in the evolution of H 2 S-based therapy that facilitate clinical translation to patients are discussed.

Nanozymes with the merits of effective enzyme-mimic activities, tunable catalytic properties, pH/temperature tolerance, and high stability have been consumingly researched for nanocatalytic therapy. Herein, the union nanozymes and a natural enzyme nanoplatform (DMSN@CoFe 2 O 4 /GOD-PCM) are elaborately designed by simply depositing an ultrasmall cobalt ferrite (CoFe 2 O 4 ) bimetallic oxide nanozyme and natural glucose oxidase (GOD) that are loaded into the aperture (∼12 nm) of dendritic mesoporous silica (DMSN) for near-infrared-II-enhanced tumor therapy. Upon irradiation, the hyperthermia generated by CoFe 2 O 4 nanozymes unlocks the "gate" of phase-change material (PCM) for releasing GOD, which reshapes the specific tumor microenvironment (TME) through the glucose metabolism pathway. The resulting strengthened acid condition and a considerable amount of H 2 O 2 efficiently initiate the cascade catalysis reactions. Moreover, highly toxic hydroxyl radicals are generated with a Co/Fe dual-cycle system of ultrasmall CoFe 2 O 4 nanozymes. The in situ glutathione consumption and hypoxia relief further amplify oxidative stress. In addition, chemotherapeutic effects due to the cytotoxicity of cobalt ions enhance the therapeutic performance. Collectively, this study provides a proof of concept for TME-reshaped natural and artificial nanozyme cascade catalysis for combined reactive oxygen species-based therapy and chemotherapy.

No abstract