Sono-Driven Sting Activation Using Semiconducting Polymeric Nanoagonists For Precision Sono-Immunotherapy of Head And Neck Squamous Cell Carcinoma

by Selleckchem | Sep 19 2023

Immunotherapy has offered new opportunities to treat head and neck squamous cell carcinoma (HNSCC); however, its clinical applications are hindered by modest therapeutic outcomes and the "always-on" pharmacological activity of immunomodulatory agents. Strategies for precise spatiotemporal activation of antitumor immunity can tackle these issues but remain challenging. Herein, we report a semiconducting polymeric nanoagonist (SPNM) with in situ sono-activatable immunotherapeutic effects for precision sono-immunotherapy of HNSCC. SPNM is self-assembled from a sonodynamic semiconducting polymer core conjugated with a stimulator of interferon genes (STING) agonist (MSA-2) via a singlet oxygen cleavable linker. Under sono-irradiation, SPNM produces singlet oxygen not only to eradicate tumor cells to trigger immunogenic cell death but also to unleash caged STING agonists via the cleavage of diphenoxyethene bonds for in-situ activation of the STING pathway in the tumor region. Such sono-driven STING activation mediated by SPNM promotes effector T cell infiltration and potentiates systemic antitumor immunity, eventually leading to tumor growth inhibition and long-term immunological memory. This study thus presents a promising strategy for the precise spatiotemporal activation of cancer immunotherapy.

Comments:

The provided excerpt describes a research study that proposes a new approach for the treatment of head and neck squamous cell carcinoma (HNSCC) using immunotherapy. While immunotherapy has shown promise in treating HNSCC, its effectiveness has been limited, and the continuous pharmacological activity of immunomodulatory agents can be problematic. The researchers introduce a novel approach using a semiconducting polymeric nanoagonist (SPNM) that can be activated precisely in space and time using ultrasound (sono-activation).

The SPNM is composed of a core made from a sonodynamic semiconducting polymer, which generates singlet oxygen upon sono-irradiation. This singlet oxygen serves two purposes: firstly, it helps eradicate tumor cells through immunogenic cell death, which triggers an immune response. Secondly, the SPNM is conjugated with a stimulator of interferon genes (STING) agonist (MSA-2) through a cleavable linker. Under sono-irradiation, the singlet oxygen produced by SPNM cleaves the linker, releasing the STING agonist, which can activate the STING pathway in the tumor region. Activation of the STING pathway promotes the infiltration of effector T cells and enhances systemic antitumor immunity. Consequently, this approach leads to the inhibition of tumor growth and the development of long-term immunological memory.

The study suggests that this sono-activatable immunotherapeutic strategy utilizing SPNM can overcome the limitations of traditional immunotherapy for HNSCC. By precisely controlling the activation of the immune response within the tumor region, the researchers hope to achieve better therapeutic outcomes. However, it is important to note that the provided excerpt is an abstract or summary of a research article, and the full study would contain more detailed information on the experimental design, results, and limitations of the research.