Affiliation:
1. State Key Laboratory of Systems Medicine for Cancer Renji‐Med X Clinical Stem Cell Research Center Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China
2. Institute of Molecular Medicine (IMM) Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai 200127 China
3. Evergrande Center for Immunologic Diseases Ann Romney Center for Neurologic Diseases Harvard Medical School and Mass General Brigham Boston MA 02115 USA
Abstract
AbstractTumor 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.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
School of Medicine, Shanghai Jiao Tong University
Innovative Research Team of High-level Local University in Shanghai
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)