Engineered photothermal-responsive bacterial platform for in vivo fluorescence imaging-guided photothermal/gene combined breast cancer therapy

By leveraging the capacity of near-infrared light to penetrate deep tissue, we devised an engineered bacterial system for fluorescence imaging-guided photothermal/gene combined cancer therapy. By incorporating a thermosensitive plasmid carrying a payload of cytolysin A (ClyA) into the probiotic Escherichia coli Nissle 1917 (EcN) and incubating it with the photothermal agent indocyanine green (ICG)/Cremophor EL, we generated engineered bacteria capable of photothermal conversion. Upon irradiation with a near-infrared laser, ICG within the engineered bacterial cells converted them into localized heat above 42°C. This simultaneous photothermal therapy cleverly activated the expression of the therapeutic protein ClyA, resulting in the synergistic killing of tumor cells. Importantly, as a natural immune adjuvant, EcN enhanced the body's immune response. In addition, the engineered bacteria exhibited significant cytotoxic effects on tumor cells and suppressed tumor growth. Our study demonstrates a near-infrared laser-controlled bacterial platform that can be applied to precision cancer therapeutics.