Engineered Microbial Nanohybrids for Tumor‐Mediated NIR II Photothermal Enhanced Ferroptosis/Cuproptosis and Immunotherapy

Abstract

AbstractThe colon tumor microenvironment has a high concentration of H2S and glutathione, which is highly immunosuppressive and adverse to multiple therapeutic methodologies such as ferroptosis. Here, an engineered microbial nanohybrid based on Escherichia coli (E. coli) and Cu2O nanoparticles to specific colon tumor therapy and immunosuppression reversion is reported. The as‐prepared E. coli@Cu2O hybrid can accumulate in tumor sites upon intravenous injection, and Cu2O nanoparticles convert to CuxS by consuming the endogenous H2S, which exhibits strong photothermal conversion at near‐infrared II (NIR II) biological window. Furthermore, E. coli@Cu2O is able to induce cellular ferroptosis and cuproptosis through inactivation of glutathione peroxidase 4 and aggregation of dihydrolipoamide S‐acetyltransferase, respectively. Photothermal‐enhanced ferroptosis/cuproptosis achieved by E. coli@Cu2O reverses the immunosuppression of colon tumors by triggering dendritic cell maturation (about 30%) and T cell activation (about 50% CD8+ T cells). Concerted with immune checkpoint blockade, the engineered microbial nanohybrid can inhibit the growth of abscopal tumors upon NIR illumination. Overall, the designed microbial nanohybrid can achieve tumor‐specific photothermal‐enhanced ferroptosis/cuproptosis and immunosuppression reversion, showing promise in precise tumor therapy in future clinical translation.