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 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 (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 1 O2 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.

• Authors: Mengke Xu, Jie Yu, Chi Zhang, Cheng Xu, Xin Wei, Kanyi Pu
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 62 Issue 40 Pg. e202308362 (10 02 2023) ISSN: 1521-3773 [Electronic] Germany
• PMID: 37587095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 Wiley-VCH GmbH.

Chemical References

• Cytokines
• Interleukin-2

Topics

• Humans
• Cytokines (metabolism)
• Interleukin-2
• T-Lymphocytes, Regulatory (metabolism)
• Immunotherapy (methods)
• Neoplasms (drug therapy)
• Tumor Microenvironment
• Cell Line, Tumor