Engineered Bioluminescent Nano-Bacteria Biohybrids Powering Self-Driven Photodynamic and Photothermal Synergistic Cancer Treatment

Photodynamic therapy (PDT) is a clinically effective antitumor treatment offering spatiotemporal precision, minimal invasiveness, and low systemic toxicity. However, its application is limited by the shallow penetration of external light sources, particularly for deep-seated tumors. Moreover, PDT alone often fails to fully inhibit tumor growth, prompting its combination with other modalities such as photothermal therapy (PTT), which induces tumor cell death through localized heating. In this study, we developed a nano-bacteria biohybrid, EcN-QS-iLux@Pd@MC540, by biomineralizing the engineered probiotic <i>Escherichia coli</i> Nissle 1917 (EcN-QS-iLux) with palladium nanoparticles and loading it with the photosensitizer MC540. This biohybrid performs self-driven PDT without external light and effective PTT under 808 nm light excitation. In vivo studies using a 4T1 tumor mouse model demonstrated complete tumor inhibition through the synergistic action of PDT and PTT, with no significant systemic toxicity. This platform showcases the use of nano-bioluminescent bacteria to integrate self-driven PDT with synergistic PTT, providing a targeted and minimally invasive strategy for cancer therapy.