文献类型：期刊文献

英文题名：Self-Adjusting Engineered Probiotic for Targeted Tumor Colonization and Local Therapeutics Delivery

作者：Zou, Zhen-Ping[1];Wang, Xin-Ge[1];Shi, Xuan-Ren[1];Sun, Shu-Ting[1];Mi, Jing[1];Zhang, Xiao-Peng[1];Yin, Bin-Cheng[1];Zhou, Ying[1];Ye, Bang-Ce[1,2]

机构：[1]East China Univ Sci & Technol, Lab Biosyst & Microanal, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Zhejiang Univ Technol, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gre, Inst Engn Biol & Hlth, Hangzhou 310014, Zhejiang, Peoples R China

年份：2025

卷号：12

期号：31

外文期刊名：ADVANCED SCIENCE

收录：;EI(收录号：20252218517576);WOS:【SCI-EXPANDED(收录号:WOS:001556225800024)】；

基金：This work was sponsored by the National Natural Science Foundation of China (22134003), the National Key Research and Development Program of China (2020YFA0908800 and 2023YFF1204500) and China Postdoctoral Science Foundation (2023M741176, 2024T170274). The authors were grateful to LC Bio Technology CO., Ltd. for assisting in Mass spectrometry detection and bioinformatics analysis.

语种：英文

外文关键词：engineered probiotics; multiplexed; self-adjusting; synthetic biology; tumors treatment

摘要：Engineered bacteria have demonstrated great potential for treating a broad array of tumors. However, the precision and safety of controlling the performance of engineered bacteria in vivo remains a central challenge. Here, genetic circuit programming strategy is utilized to construct an engineered Escherichia coli Nissle 1917 with accurate targeted colonizing and on-demand payloads releasing ability. The engineered probiotic survives only in the presence of more than 5 mM L-lactate by employing an improved lactate-sensing system, which leads to preventing the growth outside the permissive environments in mice. Meanwhile an expressing alpha-hemolysin (SAH) circuit based on quorum-sensing system is introduced to augment anti-tumor effect. Furthermore, coagulase (Coa) induced by high-level lactate creates the closure to deprive tumor of nutrients and oxygen and may help prevent the leakage of bacteria and SAH, which enhances the therapeutic effectiveness and biosafety. This self-adjusting living biotherapeutics significantly inhibits tumor proliferation and prolongs the survival time of colorectal tumor-bearing mice. Together, this work takes a step toward safer and more effective application of living bacteria for tumor treatment in practice.