Open AccessBacteria‐Elicited Specific Thrombosis Utilizing Acid‐Induced Cytolysin A Expression to Enable Potent Tumor Therapy
Author(s) -
Qin Wenjun,
Xu Wenxuan,
Wang Longyu,
Ren Debao,
Cheng Yibin,
Song Wen,
Jiang Tao,
Ma Lixin,
Zhang Cheng
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202105086
Subject(s) - cytolysin , bacteria , oncolytic virus , cancer research , thrombosis , microbiology and biotechnology , medicine , chemistry , biology , tumor cells , biochemistry , gene , genetics , virulence
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.