Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy

Polymeric STING pro-agonists for tumor-specific sonodynamic immunotherapy

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) w...

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Bibliographic Details
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
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Institution: Nanyang Technological University
Language: English
Description
Summary: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.

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