A biomimetic nanodisc system selectively activates type I interferons by nonclassical STING pathway for cancer immunotherapy

  • Nat Commun. 2026 Mar 31. doi: 10.1038/s41467-026-71363-6.
Qianwen Mu  #  1  2  3 ,  Haolan Deng  #  1  2 ,  Shuo Li  #  1 ,  Xiaoyu An  1  2 ,  Xuan Liu  2 ,  Yue Xi  1 ,  Hao Liang  1 ,  Di Sun  1 ,  Xiaojun Wang  1 ,  Xue Liu  2 ,  Gang Liu  4  5 ,  Chao Liu  6  7  8
Affiliations
  • 1. Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
  • 2. Fujian Engineering Research Center of Molecular Theranostic Technology, School of Public Health, Xiamen University, Xiamen, China.
  • 3. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
  • 4. Fujian Engineering Research Center of Molecular Theranostic Technology, School of Public Health, Xiamen University, Xiamen, China. [email protected].
  • 5. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China. [email protected].
  • 6. Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China. [email protected].
  • 7. Fujian Engineering Research Center of Molecular Theranostic Technology, School of Public Health, Xiamen University, Xiamen, China. [email protected].
  • 8. Shenzhen Research Institute of Xiamen University, Shenzhen, China. [email protected].
  • # Contributed equally.
PMID: 41917023 DOI: 10.1038/s41467-026-71363-6
Abstract

The epigenetic silencing or remarkably diminished expression of STING in Cancer cells, along with the structural and functional impairment of the endoplasmic reticulum (ER) and Golgi apparatus, represents a unique mechanism of tumor immune escape and poses an important challenge for STING-targeted therapies. Here, we develop a cell membrane-derived nanodisc system (ND-cGAMP-HP; HP, heparin), which is capable of presenting activated STING proteins in their native form by means of cell membrane-directed display and biological self-assembly techniques. It can directly introduce activated STING protein to tumor cells and circumvent the translocation process between the ER and Golgi apparatus, selectively activating the IFN-I signaling pathway without initiating the inflammation-related pathway NF-κB. ND-cGAMP-HP triggers potent cellular immune responses and remodels the tumor immune microenvironment. Moreover, it augments immune memory by promoting the differentiation of TCF1+ stem cell-like T cells. We thus manifest a strategy based on STING therapy that does not depend on the ER and Golgi apparatus pathways to activate the IFN-I pathway, for Cancer Immunotherapy.

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