Given the special microenvironment of solid tumors, live microorganisms have emerged as drug delivery vehicles and therapeutic agents. Here, an acid-induced therapeutic platform is constructed using attenuated Escherichia coli to express the cytolysin A protein. The bacteria can target and colonize tumor tissues without causing notable host toxicity. Bacterial infection can disrupt blood vessels and trigger thrombosis in tumor tissues, resulting in the cut-off of nutrient supply to tumor cells and the arrest of tumor growth. The expression of cytolysin A induced by the acidic tumor microenvironment further strengthens thrombosis and provides a complementary therapeutic option due to its pore-forming function. In a xenograft mouse tumor model, this strategy reduces tumor proliferation by 79% and significantly prevents tumor metastasis, thus paving a new avenue for bacteria-based tumor therapy.

Statistical Analysis: Statistical analyses were performed using GraphPad Prism. Data were obtained from at least three independent measurements and are shown as mean ± standard deviation, unless otherwise indicated. Statistical significance was calculated using one-way ANOVA with Tukey's post hoc test; ** p < 0.01 and *** p < 0.001 were considered statistically significant.

The special microenvironment of solid tumor promotes the orientation and colonization of facultative anaerobe. Intratumoral bacterial infection disrupts the local vascular to form thrombosis, resulting in dimmed tumor sites and...