Photothermally Triggered Bacterial-Manganese Immune Amplifier Enables Spatiotemporal STING Hyper-Activation against Cold Tumors.

Abstract

Cold tumors suffer from insufficient innate immune priming. To overcome this, we construct a photothermally programmable bacterial-metal immune amplifier (Bac@IR780@MnTA). This hybrid material is sequentially assembled by anchoring IR780 onto interferon-β (IFN-β)-expressing <i>Escherichia coli</i>, followed by the <i>in situ</i> deposition of a manganese-tannic acid (MnTA) coordination shell. Near-infrared irradiation simultaneously induces tumor DNA damage and immunogenic cell death, functioning as a precise thermal switch for the on-demand expression of bacterial IFN-β and synchronized release of Mn²⁺. These coupled signals establish a feed-forward cascade: Mn²⁺ lowers the cGAS activation threshold to hyper-activate the STING pathway, while exogenous IFN-β reinforces type I interferon signaling. <i>In vivo</i>, this system effectively reprograms the immunosuppressive microenvironment, enhances dendritic cell maturation, and recruits CD8⁺ T cells to drive systemic antitumor immunity, establishing a robust material-engineered paradigm for cold-to-hot tumor conversion.