Research Article | Open Access
Volume 2024 |Article ID 0038 |

Lipid-Encapsulated Engineered Bacterial Living Materials Inhibit Cyclooxygenase II to Enhance Doxorubicin Toxicity

Ning Jiang,1,2 Wanqing Ding,1,2 Xiaojuan Zhu,1,2 Jianshu Chen,1,2 Lin Yang,3 Xiaoping Yi,1 Yingping Zhuang,1,2 Jiangchao Qian,1 Jiaofang Huang 1,3

1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology(ECUST), Shanghai 200237, China
2Shanghai Collaborative Innovation Center for Biomanufacturing(SCICB), East China University of Science and Technology, Shanghai 200237, China
3College of LifeScience, Jiangxi Normal University (JXNU), Nanchang 330022, China

24 Mar 2024
28 Apr 2024
25 Jun 2024


Recently, there has been increasing interest in the use of bacteria for cancer therapy due to their ability to selectively target tumor sites and inhibit tumor growth. However, the complexity of the interaction between bacteria and tumor cells evokes unpredictable therapeutic risk, which induces inflammation, stimulates the up-regulation of cyclooxygenase II (COX-2) protein, and stimulates downstream antiapoptotic gene expression in the tumor microenvironment to reduce the antitumor efficacy of chemotherapy and immunotherapy. In this study, we encapsulated celecoxib (CXB), a specific COX-2 inhibitor, in liposomes anchored to the surface of Escherichia coli Nissle 1917 (ECN) through electrostatic absorption (C@ECN) to suppress ECN-induced COX-2 up-regulation and enhance the synergistic antitumor effect of doxorubicin (DOX). C@ECN improved the antitumor effect of DOX by restraining COX-2 expression. In addition, local T lymphocyte infiltration was induced by the ECN to enhance immunotherapy efficacy in the tumor microenvironment. Considering the biosafety of C@ECN, a hypoxia-induced lysis circuit, pGEX-Pvhb-Lysis, was introduced into the ECN to limit the number of ECNs in vivo. Our results indicate that this system has the potential to enhance the synergistic effect of ECN with chemical drugs to inhibit tumor progression in medical oncology.

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