X-Ray-Responsive Engineered Bacteria for Synergistic Radioimmunotherapy and Photoacoustic Immunomonitoring of Triple-Negative Breast Cancer.

Engineered bacteria offer promising opportunities for cancer immunotherapy, yet precise in vivo activation and real-time tracking of immune responses remain formidable challenges. Here, we present an x-ray-sensitive engineered bacterium, composed of Escherichia coli (E. coli) and gold-silver nanorods (Ec-GS NRs), for synergistic radioimmunotherapy and photoacoustic (PA) immunomonitoring of triple-negative breast cancer (TNBC). Upon x-ray irradiation, Ag+ release induces bacterial damage, stimulating the host immune system and triggering immunogenic tumor cell death. Moreover, radiation-induced etching alters nanorod optoacoustic properties, enabling noninvasive PA monitoring of immunotherapy initiation. In TNBC models, Ec-GS NRs combined with x-ray irradiation achieved near-complete tumor regression through enhanced radioimmunotherapy. Concurrently, PA signal ratio (PA808/PA1064) increased 127-fold, allowing in situ monitoring of immune activation. Notably, Ec-GS NRs elicited a strong abscopal effect, suppressing distant metastases and extending overall survival. This study thus establishes a bacteria-enabled radioimmunotheranostic strategy integrating x-ray-controllable immune activation, radiosensitization, and PA-immunomonitoring to address limitations in precision cancer therapy.