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

Author:

Jiang Ning12,Ding Wanqing12,Zhu Xiaojuan12,Chen Jianshu12,Yang Lin3,Yi Xiaoping1,Zhuang Yingping12,Qian Jiangchao1,Huang Jiaofang13ORCID

Affiliation:

1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST), Shanghai 200237, China.

2. Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB), East China University of Science and Technology, Shanghai 200237, China.

3. College of Life Science, Jiangxi Normal University (JXNU), Nanchang 330022, China.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

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