Pyroptosis, a form of programmed cell death mediated by the gasdermin family, has emerged as a promising strategy for inducing anti-tumor immunity. However, efficiently inducing pyroptosis in tumor cells remains a significant challenge due to the limited activation of key mediators like caspases in tumor tissues. Herein, a self-priming pyroptosis-inducing agent (MnNZ@OMV) is developed by integrating outer membrane vesicles (OMVs) with manganese dioxide nanozymes (MnNZ) to trigger pyroptosis in tumor cells. OMVs, derived from Escherichia coli, are coated onto spiny MnNZ to prepare MnNZ@OMV. Once internalized by tumor cells, MnNZ@OMV responds to elevated intracellular glutathione (GSH) levels, releasing Mn