Sonodynamic Cytokine Nanocomplexes with Specific Stimulation towards Effector T Cell for Combination Cancer Immunotherapy
Mengke Xu, Jie Yu, Chi Zhang, Cheng Xu, Xin Wei, Kanyi Pu
Abstract
Abstract Cytokine therapy mediates the interaction between immune cells and non‐immune cells in the 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 (SPN AI ) 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 SPN A , this nanoantibody SPN A can bind with IL‐2 to form SPN AI which can block the interaction between IL‐2 and regulatory T cells (Tregs), selectively activating Teffs in TME. Moreover, SPN AI generates 1 O 2 to trigger immunogenic cell death of cancer cells upon sono‐irradiation, which promotes the maturation of dendritic cells and the proliferation of Teffs. This SPN AI ‐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.