Precise Thermal Regulation of Engineered Bacteria Secretion for Breast Cancer Treatment In Vivo

For the biomedical application of engineered bacteria, strictly regulating the function of engineered bacteria has always been the goal pursued. However, the existing regulation methods do not meet the needs of the in vivo application of engineered bacteria. Therefore, the exploration of the precise regulation of engineered bacteria is necessary. Herein, heat-sensitive engineered bacteria that can respond to thermal stimuli within 30 min were constructed, and the precise control of functions was verified in the intestines of various model organisms (including C. elegans, bees, and mice). Subsequently, heat-sensitive engineered bacteria were shown to colonize the mouse tumor microenvironment. Finally, thermal stimulation was proven to control engineered bacteria to produce the therapeutic protein tumor necrosis factor α (TNF-α) in the tumor. After three heat stimulation treatments, the growth of the tumor was significantly inhibited, suggesting that heat can be used as a strategy to precisely control engineered bacteria in vivo.