Sonodynamic Cytokine Nanocomplexes with Specific Stimulation towards Effector T cell for Combination Cancer Immunotherapy.

Abstract

Cytokine therapy mediates the interaction between immune cells and non-immune cells in tumor microenvironment (TME), forming a promising approach in cancer therapy. However, the dose-dependent adverse effects and non-selective stimulation of cytokines limit their clinical use. We herein report a sonodynamic cytokine nano-immunocomplex (SPNAI) that specifically activates effector T cells (Teffs) for antitumor immunotherapy. By conjugating anti-interleukin-2 (anti-IL-2) antibodies S4B6 on the semiconducting polymer nanoparticles to afford SPNA, this nanoantibody SPNA can bind with IL-2 to form SPNAI which can block the interaction between IL-2 and regulatory T cells (Tregs), selectively activating Teffs in TME. Moreover, SPNAI generates 1O2 to trigger immunogenic cell death of cancer cells upon sono-irradiation, which promotes the maturation of dendritic cells and the proliferation of Teffs. This SPNAI-mediated combination sonodynamic immunotherapy thus elevates the ratio of Teffs/Tregs in TME, resulting in inhibition of tumor growth, suppression of lung metastasis and prevention of tumor relapse.