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Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation

Author

Listed:
  • Kaiyuan Wang

    (Shenyang Pharmaceutical University
    National University of Singapore)

  • Yang Li

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Xia Wang

    (Shenyang Pharmaceutical University)

  • Zhijun Zhang

    (Shenzhen University)

  • Liping Cao

    (Shenyang Pharmaceutical University)

  • Xiaoyuan Fan

    (Shenyang Pharmaceutical University)

  • Bin Wan

    (Shenyang Pharmaceutical University)

  • Fengxiang Liu

    (Shenyang Pharmaceutical University)

  • Xuanbo Zhang

    (Shenyang Pharmaceutical University
    National University of Singapore)

  • Zhonggui He

    (Shenyang Pharmaceutical University)

  • Yingtang Zhou

    (Zhejiang Ocean University)

  • Dong Wang

    (Shenzhen University)

  • Jin Sun

    (Shenyang Pharmaceutical University)

  • Xiaoyuan Chen

    (National University of Singapore
    National University of Singapore
    National University of Singapore
    Agency for Science, Technology, and Research (A*STAR))

Abstract

The immunologically “cold” microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property of gas therapy with cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation to augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-based photoimmunotherapy. A virus-mimicking hollow mesoporous tetrasulfide-doped organosilica is developed for co-encapsulation of AIEgen and manganese carbonyl to fabricate gas nanoadjuvant. As tetra-sulfide bonds are responsive to intratumoral glutathione, the gas nanoadjuvant achieves tumor-specific drug release, promotes photodynamic therapy, and produces hydrogen sulfide (H2S). Upon near-infrared laser irradiation, the AIEgen-mediated phototherapy triggers the burst of carbon monoxide (CO)/Mn2+. Both H2S and CO can destroy mitochondrial integrity to induce leakage of mitochondrial DNA into the cytoplasm, serving as gas immunoadjuvants to activate cGAS-STING pathway. Meanwhile, Mn2+ can sensitize cGAS to augment STING-mediated type I interferon production. Consequently, the gas nanoadjuvant potentiates photoimmunotherapy of poorly immunogenic breast tumors in female mice.

Suggested Citation

  • Kaiyuan Wang & Yang Li & Xia Wang & Zhijun Zhang & Liping Cao & Xiaoyuan Fan & Bin Wan & Fengxiang Liu & Xuanbo Zhang & Zhonggui He & Yingtang Zhou & Dong Wang & Jin Sun & Xiaoyuan Chen, 2023. "Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cGAS-STING pathway activation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38601-7
    DOI: 10.1038/s41467-023-38601-7
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    3. Jiaqi Yan & Xiaodong Ma & Danna Liang & Meixin Ran & Dongdong Zheng & Xiaodong Chen & Shichong Zhou & Weijian Sun & Xian Shen & Hongbo Zhang, 2023. "An autocatalytic multicomponent DNAzyme nanomachine for tumor-specific photothermal therapy sensitization in pancreatic cancer," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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