Citation: Chuangxin Zhang, Yunxia Wang, Ruipeng Li, Sirong Zhou, Liheng Feng. A multi-pronged approach to activate and amplify cGAS-STING for boosted photoimmunotherapy by drug-free nano-assembly[J]. Chinese Chemical Letters, ;2026, 37(5): 111403. doi: 10.1016/j.cclet.2025.111403 shu

A multi-pronged approach to activate and amplify cGAS-STING for boosted photoimmunotherapy by drug-free nano-assembly

Chuangxin Zhang ^a ,
Yunxia Wang ^{a, *,} ,
Ruipeng Li ^a ,
Sirong Zhou ^a ,
Liheng Feng ^{a, b, *,}

a.
School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China
b.
Institute for Carbon-Based Thin Film Electronics, Peking University, Shanxi (ICTFE-PKU), Taiyuan 030012, China

wangyunxia@sxu.edu.cn

lhfeng@sxu.edu.cn

Received Date: 17 April 2025
Revised Date: 30 May 2025
Accepted Date: 3 June 2025
Available Online: 3 June 2025

Figures(6)

The low tumor immunogenicity, high immunosuppressive microenvironment, and off-target toxicity severely limit the efficiency of the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway that plays an important role in tumor immunotherapy. We herein develop a multifunctional nano-assembly with tumor targeting, double-stranded DNA (dsDNA) releasing, Mn²⁺ sensitizing and immune microenvironment reprogramming capabilities for improving cGAS-STING to bridge innate and adaptive immunity. The drug-free nano-assembly composed of organic AIE-type photosensitizer and MnO₂ can improve the tumor immune microenvironment by consuming glutathione and producing oxygen in the presence of H₂O₂, concurrently enhancing the release of damaged dsDNA and sensitizing the cGAS by controlled release of Mn²⁺ to magnify cGAS-STING immunity. In vivo experiments reveal that the multi-mode synergistic activation of STING pathway at the headstream can not only damage the primary tumors to amplify innate immunity, but also facilitate the maturation of dendritic cells, infiltration of cytotoxic T lymphocytes and expansion of adaptive immunity to inhibit primary tumor metastasis and recurrence in the long term.
- STING pathway,
- Tumor immunotherapy,
- Photo-activation,
- Nano-assembly,
- Tumor metastasis and recurrence
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