Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy

• Main Authors: Yu, Jie, He, Shasha, Zhang, Chi, Xu, Cheng, Huang, Jingsheng, Xu, Mengke, Pu, Kanyi
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Medicine; Cancer Therapy; Immunotherapy
• Online Access: https://hdl.handle.net/10356/171012
• Institution: Nanyang Technological University

The efficacy of combination immunotherapy has been limited by tumor specificity and immune-related adverse events (irAEs). Herein, we report the development of polymeric STING pro-agonists (PSPA), whose sono-immunotherapeutic efficacy is activated by sono-irradiation and elevated glutathione (GSH) within the tumor microenvironment (TME). PSPA is composed of sonosensitizers (semiconducting polymer) and STING agonists (MSA-2) via the GSH-activatable linkers. Under sono-irradiation, PSPA serves as a sonosensitizer to generate 1 O2 and induce immunogenic cell death (ICD) of malignant tumor cells. Furthermore, MSA-2 is released specifically in tumor microenvironment with highly expressed GSH, minimizing off-target side effects. The activation of the STING pathway elevates the interferon-β level and synergizes with SDT to enhance the anti-tumor response. Therefore, this work proposes a universal approach for spatiotemporal regulation of cancer sono-immunotherapy.