Nanodrug Engineered Bacteria for Tumor-Targeted and Synergistic Photothermal Immunotherapy
Cancer immunotherapy, particularly small-molecule immune checkpoint inhibitors (ICIs), offers low cost and high tumor diffusion but suffers from limited efficacy and systemic toxicity. Here, we engineered non-pathogenic Escherichia coli MG1655 for tumor-targeted and synergistic photothermal immunotherapy. Polydopamine (PDA) was coated onto the bacterial surface via in situ polymerization, followed by noncovalent attachment of the IDO-1 inhibitor NLG919, yielding MG1655@PDA-NLG. The functionalized bacteria retained viability and bioactivity while exhibiting outstanding photothermal conversion. In a murine CT26 colon tumor model, intravenous injection led to effective tumor accumulation within 12 h and complete clearance from major organs by 72 h, with negligible hematological toxicity, confirming hypoxic tumor-targeting and biosafety. Under near-infrared irradiation, the engineered bacteria inhibited tumor growth by over 90%, combining photothermal effect and immunogenic cell death (ICD) to promote dendritic cell maturation. This synergized with suppression of tryptophan metabolism, enhancing CD4+ and CD8+ T cell infiltration. This work demonstrates a simple, safe strategy for surface engineering of bacteria with multiple therapeutic agents, offering a promising approach for precise and combined cancer immunotherapy.