Sonodynamic Cytokine Nanocomplexes with Specific Stimulation towards Effector T Cell for Combination Cancer Immunotherapy
Mengke Xu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorJie Yu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorChi Zhang
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorCheng Xu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorDr. Xin Wei
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorCorresponding Author
Prof. Kanyi Pu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636921 Singapore
Search for more papers by this authorMengke Xu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorJie Yu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorChi Zhang
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorCheng Xu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorDr. Xin Wei
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Search for more papers by this authorCorresponding Author
Prof. Kanyi Pu
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457 Singapore
Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636921 Singapore
Search for more papers by this authorAbstract
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 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.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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