Bacteria-Elicited Specific Thrombosis Utilizing Acid-Induced Cytolysin A Expression to Enable Potent Tumor Therapy

作者:Qin, Wenjun; Xu, Wenxuan; Wang, Longyu; Ren, Debao; Cheng, Yibin; Song, Wen; Jiang, Tao*; Ma, Lixin*; Zhang, Cheng*
来源:Advanced Science, 2022, 9(15): 2105086.
DOI:10.1002/advs.202105086

摘要

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.