Transformable DNA octahedron for remodeling tumor immune microenvironment with alleviated toxicity

The flexibility of DNA nanostructures offers a versatile platform for combatting tumors. In this study, a transformable DNA octahedron was constructed by incorporating acidity-responsive sequences into the architecture. Triggered by an acidic microenvironment, the loaded “nano-soldiers,” platinum-nanodrugs equipped with the immune adjuvant R848, could slip into the tumor. These soldiers fulfilled their duty of reshaping the immunosuppressive landscape by synergistically repolarizing pro-tumor M2 macrophages into anti-tumor M1 and inducing immunogenic cell death. Satisfactory therapeutic efficacy was achieved in the metastatic tumor model. An examination of the mechanism validated the efficacy of M2 macrophage repolarization, dendritic cell maturation, and CD8+ T-cell infiltration, which remodeled the immune microenvironment and maximized antitumor immune responses. Importantly, this strategy alleviated the toxicity caused by free drugs, consolidating the potential of DNA architecture as an immune therapy vehicle.