Polymeric STING Pro-agonists for Tumor-Specific Sonodynamic Immunotherapy.

Authors :: Yu J
He S
Zhang C
Xu C
Huang J
Xu M
Pu K
Source :: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Aug 07; Vol. 62 (32), pp. e202307272. Date of Electronic Publication: 2023 Jun 30.
Publication Year :: 2023
Abstract: 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 <superscript>1</superscript> O <subscript>2</subscript> 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.<br /> (© 2023 Wiley-VCH GmbH.)