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[Display omitted] • A fresh type of metal-sensitized sonocatalyst was designed. • The light/sono-responsive nanoplatform can generate adequate ROS and heat. • Generated ROS and heat mutualistically trigger immunogenic cell death. • The sonocatalyst activates immune response, hindering tumor growth and metastasis. Sonodynamic tumor therapy is limited by inefficient sonosensitizers and complex tumor microenvironments. Given this, a concept of metal-sensitized sonocatalyst is proposed and defined as a catalyst based on the metal sensitization effect of noble metals to advance semiconductor sonocatalytic activity. We load Au nanorods onto wide-bandgap semiconductor bismuth oxide to favor its sonocatalytic properties for supporting the concept's practicality. In the catalytic nano-system, Au nanorods improve the ability of bismuth oxide to separate electrons and holes under ultrasound, promoting multifarious reactive oxygen species (ROS) generation and enhancing the photothermal effect. Synergistically, bismuth oxide can consume intratumoral overexpressed glutathione, further disrupting the redox balance. Thus, ROS and heat can directly induce immunogenic cell death, reversing tumor immunosuppressive microenvironment in concert and promoting dendritic cell maturation and CD8+ T cell infiltration. The proposed metal-sensitized sonocatalyst will open up new avenues for sonocatalytic therapy. [ABSTRACT FROM AUTHOR]

• CuS nanosheet is a highly efficient ultrasound-controllable catalytic material. • Ultrasound-activated CO and ROS can trigger immunogenic cell death. • Oxygen generation relieves tumor hypoxia and reverses immunosuppression. Ultrasound-activated tumor catalytic therapy has great potential in clinical cancer treatment. However, the hypoxic and immunosuppressive tumor microenvironment impairs the efficacy of solid tumor treatment, leading to a high recurrence rate of metastatic cancer. Thus, reversing the tumor microenvironment remains a formidable challenge. To circumvent these critical issues, we employ ultrasound-activable carbon monoxide (CO) gas therapy and reactive oxygen species (ROS) production to trigger immunogenic cell death (ICD) and alleviate tumor hypoxia, achieving a combination of tumor therapy and reversal of immunosuppression to overcome the limitations of monotherapy and control tumor metastasis and recurrence. In brief, we first use copper sulfide (CuS) nanosheet as a highly efficient ultrasound-controllable catalytic nanomaterial, which can catalyze carbon dioxide, water, and oxygen to produce CO, oxygen, and ROS. Moreover, as a Fenton-like catalyst, it can catalyze hydrogen peroxide at tumor sites to generate ROS. The generated CO can attack mitochondria to accelerate their metabolism and produce more ROS, thus inducing ICD. In addition, the generation of oxygen can not only serve as the source of ROS, but it can also relieve tumor hypoxia and normalize the tumor immunosuppressive microenvironment. This results in the maturation of dendritic cells and the enhancement of T-lymphocyte recruitment and infiltration, further stimulating the antitumor immune response, mediating the regression of primary and distal tumors, and inhibiting lung metastasis. This in situ sono-activable catalytic therapy strategy minimizes the toxicity of CO and ROS leakage and provides a novel approach for designing new ICD inducers and improving therapeutic effects. [ABSTRACT FROM AUTHOR]