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

Abstract

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 H2 O2 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.