Light Triggered “Bacterial Bomb” to Amplify Tumor Pyroptosis

Abstract Pyroptosis is gaining attention for its ability to activate the immune system. However, controlling the induction of specific pyroptotic tumor cell death to effectively activate the immune response is a challenge. In this study, a novel “bacterial bomb” platform is developed and designed to precisely regulate tumor cell pyroptosis using light as a trigger, thereby optimizing immune responses. The platform employs Escherichia coli (Ec) as a carrier to introduce gasdermin D (GSDMD) plasmid (pGSDMD) into Ec and adsorb photosensitizer indocyanine green (ICG) on its surface, termed as Ec‐pGSDMD‐ICG. ICG has photothermal effects (PTE) and photodynamic effects (PDE). Under 808 nm laser irradiation, ICG generates thermal effects and singlet oxygen ( ¹ O ₂ ), leading to Ec rupture and the release of pGSDMD, which expresses sufficient GSDMD in tumor cells. Furthermore, ¹ O ₂ and lipopolysaccharides (LPS) of Ec activate caspase pathways (caspase‐1 and caspase‐11), which cleave GSDMD to produce GSDMD‐N, thereby inducing pyroptosis and immune responses. Light triggered Ec‐pGSDMD‐ICG not only efficiently induces pyroptosis in tumor cells with low GSDMD content, but also enhances the pyroptosis in tumor cells with moderate GSDMD content, all while activating the immune system for effective tumor treatment. This approach opens new strategies and research directions for pyroptosis mediated tumor immunotherapy.