A Single-atom Manganese Nanozyme Mn-N/C Promotes Anti-tumor Immune Response via Eliciting Type I Interferon Signaling

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 we construct a single-atom manganese (Mn)-N/C nanozyme. 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 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, Mn-N/C-triggered releasing of cytosolic DNA from ICD tumor cells activates cGAS-STING pathway, consequently stimulating type I IFN induction. We propose a new promising single-atom nanozyme with extraordinary catalytic activity, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with anti-PD-L1 blockade. Overall design: Comparative gene expression profiling analysis of RNA-seq data for tumor tissues treated with saline or Mn-N/C