DOI: 10.1002/advs.202305979 ISSN: 2198-3844

A Single‐Atom Manganese Nanozyme Mn‐N/C Promotes Anti‐Tumor Immune Response via Eliciting Type I Interferon Signaling

Wen Qiao, Jingqi Chen, Huayuan Zhou, Cegui Hu, Sumiya Dalangood, Hanjun Li, Dandan Yang, Yu Yang, Jun Gui
  • General Physics and Astronomy
  • General Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Materials Science
  • General Chemical Engineering
  • Medicine (miscellaneous)


Tumor microenvironment (TME)‐induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single‐atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single‐atom manganese (Mn)‐N/C nanozyme is constructed. Mn‐N/C catalyzes the conversion of cellular H2O2 to ∙OH through a Fenton‐like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti‐tumor immunity. Moreover, RNA sequencing analysis reveals that Mn‐N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn‐N/C‐mediated anti‐tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn‐N/C collectively activates the cGAS‐STING pathway, subsequently stimulating type I IFN induction. A highly efficient single‐atom nanozyme, Mn‐N/C, which enhances anti‐tumor immune response and exhibits synergistic therapeutic effects when combined with the anti‐PD‐L1 blockade, is proposed.

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