A New Sono‐Chemo Sensitizer Overcoming Tumor Hypoxia for Augmented Sono/Chemo‐Dynamic Therapy and Robust Immune‐Activating Response

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Novel sonosensitizers with intrinsic characteristics for tumor diagnosis, efficient therapy, and tumor microenvironment regulation are appealing in current sonodynamic therapy. Herein, a manganese (Mn)‐layered double hydroxide‐based defect‐rich nanoplatform is presented as a new type of sono‐chemo sensitizer, which allows ultrasound to efficiently trigger reactive oxygen species generation for enhanced sono/chemo‐dynamic therapy. Moreover, such a nanoplatform is able to relieve tumor hypoxia and achieve augmented singlet oxygen production via catalyzing endogenous H2O2 into O2. On top of these actions, the released Mn2+ ions and immune‐modulating agent significantly intensify immune activation and reverse the immunosuppressive tumor microenvironment to the immunocompetent one. Consequently, this nanoplatform exhibits excellent anti‐tumor efficacy and effectively suppresses both primary and distant tumor growth, demonstrating a new strategy to functionalize nanoparticles as sono‐chemo sensitizers for synergistic combination cancer therapy.