Sono-catalytic Nanorod-Adjuvanted In Situ Cancer Vaccine Augments 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 by low immunogenicity of tumor and the immunosuppressive tumor microenvironment. Herein, we developed an amorphous manganese-doped IrTe2 nanosonosensitizer (IrTex-Mn) to augment the sonodynamic activity and immunogenicity, thereby enhancing anti-tumor T cell immunity and reversing the immunosuppressive environment. Under ultrasound (US) irradiation, IrTex-Mn significantly enhanced the production of reactive radicals, including singlet oxygen (1O2) and hydroxyl radicals (·OH) by breaking the Ir-Te and Mn-Te bonds. The transfer of activated electrons occurred under ultrasonication at IrTex-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 CD8+ T cells in tumor site. In vivo experiments demonstrated that IrTex-Mn combined with US effectively inhibited tumor growth with a 90 % tumor inhibition rate, which was almost twice of that by IrTe2 under US irradiation (50 %). The engineered IrTex-Mn exhibited well tolerated biosafety profile. This work provided an unprecedented amorphous nanosonosensitizer platform for enhanced in situ cancer vaccination against tumor.