Programmable DNAzyme nanocatalysts orchestrate redox-immune coupling for time-gated cancer immunomodulation

release to induce sequence-specific catalytic cleavage of catalase mRNA. This reaction amplifies intracellular reactive oxygen species while depleting glutathione, leading to mitochondrial membrane depolarization, energetic collapse, and cytosolic release of mitochondrial DNA. The resulting mtDNA leakage activates the cGAS-STING pathway and induces a robust type I interferon response, thereby establishing a transient 4-6 h redox sensitization window. Leveraging this temporally confined state enhances dendritic-cell maturation and cytotoxic T-cell infiltration when immune checkpoint blockade is applied within the defined window. Conceptually, this work demonstrates that programmable DNAzyme catalysis can be harnessed to generate actionable temporal biochemical cues, providing a nanobiotechnology framework for time-guided innate immune modulation and highlighting the broader potential of DNAzyme-based nanocatalysts in dynamic cancer immunotherapy .