Sono-catalytic nanorod-adjuvanted in situ cancer vaccines augment antitumor T cell immunity through potentiated immunomodulation

Abstract

In situ cancer vaccination mediated by sonodynamic therapy (SDT) has demonstrated considerable potential; however, its efficacy is often suboptimal owing to the low immunogenicity of tumors and the immunosuppressive tumor microenvironment. Herein, we developed an amorphous manganese-doped IrTe₂ (IrTe_x–Mn) nanosonosensitizer to augment the sonodynamic activity and immunogenicity, thereby enhancing anti-tumor T cell immunity and reversing the immunosuppressive environment. Under ultrasound (US) irradiation, IrTe_x–Mn significantly enhanced the production of reactive radicals including singlet oxygen (¹O₂) and hydroxyl (˙OH) radicals by breaking the Ir–Te and Mn–Te bonds. The transfer of activated electrons occurred under ultrasonication at the IrTe_x–Mn–liquid interface to accelerate the chemical reactions for free radical production. Synergistically, the released Mn²⁺ ions activated the cGAS-STING pathway, promoting dendritic cell (DC) maturation and ultimately enhancing the infiltration of CD8⁺ T cells into tumor sites. In vivo experiments demonstrated that IrTe_x–Mn combined with US effectively inhibited tumor growth with a tumor inhibition rate of 90%, which was almost twice that (50%) of IrTe₂ under US irradiation. The engineered IrTe_x–Mn nanosonosensitizer exhibited a well-tolerated biosafety profile. This work provides an unprecedented amorphous nanosonosensitizer platform for enhanced in situ cancer vaccination against tumors.