Bioorthogonal Engineering of Bacterial Outer Membrane Vesicles for NIR-II Fluorescence Imaging-Guided Synergistic Enhanced Immunotherapy

1917 (Ecn) to produce DPG-functionalized OMVs, which were subsequently conjugated with azide-functionalized new indocyanine green (IR820) to yield OMV-DPG-IR820. The combination of phototherapy and immunostimulation of OMV-DPG-IR820 effectively arouses adaptive immune responses, causing maturation of dendritic cells, infiltration of T cells, repolarization of the M2 macrophage to the M1 macrophage, and upregulation of inflammatory factors. Remarkably, OMV-DPG-IR820 demonstrated tumor-targeting capabilities with guidance provided by near-infrared II (NIR-II) fluorescence imaging, leading to remarkable inhibition on both primary and distant tumors and preventing metastasis without causing noticeable adverse reactions. This study elucidates a sophisticated bioorthogonal engineering strategy for the design and production of functionalized OMVs and provides novel perspectives on the microbiome-mediated reversal of TNBC through a precise and efficient immunotherapy.