Biomineralized Engineered Bacterial Outer Membrane Vesicles as cGAS-STING Nanoagonists Synergize with Lactate Metabolism Modulation to Potentiate Immunotherapy

The immunosuppressive tumor microenvironment (TME) significantly limits the efficacy of cancer immunotherapy. Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) stimulator of interferon genes (STING) pathway and depletion of the tumor metabolic byproduct lactate (LA) represent promising strategies to reverse the immunosuppressive TME and enhance antitumor therapeutic outcomes. Herein, biomineralized engineered bacterial outer membrane vesicles (OMVs@MnCaP-FA) are developed to synergistically activate the cGAS-STING pathway and modulate LA metabolism for antitumor immunotherapy. Upon internalization by 4T1 tumor cells, OMVs@MnCaP-FA undergo acid-responsive degradation,…

• NN
  National Natural Science Foundation of China

  Awards: 22135005, 52473145, 52333004, 52131302, 52273301
• NK
  National Key Research and Development Program of China

  Award: 2022YFB3804600
• SA
  Science and Technology Program of Hubei Province

  Award: 2024DJA011