文献类型：期刊文献

英文题名：Tumor microenvironment responsive multifunctional smart living materials based on engineered bacteria for inducing macrophage polarization to enhance tumor immunotherapy

作者：Jiang, Ning[1,2];Zhao, Kui[1,2];Liu, Chengcheng[3];Zhu, Xiaojuan[1,2];Huang, Xumeng;Yang, Lin[4];Yi, Xiaoping[1];Zhuang, Yingping[1,2];Ye, Bangce[1];Qian, Jiangchao[1];Huang, Jiaofang[1,4,5]

机构：[1]East China Univ Sci & Technol ECUST, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg SCICB, Shanghai 200237, Peoples R China;[3]Xian Jiao Tong Univ Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathogen Microbiol & Immunol, 76 West Yanta Rd, Xian 710061, Peoples R China;[4]Jiangxi Normal Univ JXNU, Coll Life Sci, Nanchang 330022, Peoples R China;[5]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2024

卷号：488

外文期刊名：CHEMICAL ENGINEERING JOURNAL

收录：;EI(收录号：20241816011031);WOS:【SCI-EXPANDED(收录号:WOS:001238478000001)】；

基金：This work was supported by the National Key Research and Devel- opment Program of China (Grant No. 2020YFA0908900) , the Natural Science Foundation of Shanghai (Grant No. 22ZR1416000) , and the Fundamental Research Funds for Central Universities. We also thank the Research Center of Analysis and Test (ECUST) for their help with data collection and characterization. We thank Professor Fener Chen (JXNU) , Xianjun Chen, Rui Wang and Feng Gao (ECUST) for their help and comments.

语种：英文

外文关键词：Biomaterials; Biotechnology; Engineered living material; Targeted therapy; Drug delivery

摘要：The utilization of bacteria as a drug delivery system represents a promising strategy for tumor therapy, owing to their inherent ability to selectively colonize and induce apoptosis of tumor cells at the solid tumor. However, the occurrence of dose -dependent toxicity has led to the failure of clinical trials. Unfortunately, the implementation of a singular bacterial treatment strategy for tumor therapy is inherently limited. In this study, we developed a living drug delivery material named DOX@TA@ECN (D@T@E) by utilizing Fe 3 + and tannin acid (TA) as a crosslinking network to encapsulate doxorubicin (DOX) and form a protective coating on the surface of Escherichia coli Nissle 1917 (ECN). In an acidic tumor microenvironment, D@T@E disintegrated the coating to release DOX through the highly expressed H 2 O 2 . To enhance biosafety, the D@T@E was equipped with a hypoxic lytic circuit (Pvhb-Lysis) to regulate the number of ECN in vivo (D@T@E-PL). The hypoxic promotor of Vitreoscilla hemoglobin protein (Pvhb) were activied to induce expression of lysis protein (PhiX174E) in the tumor hypoxic microenvironment (3 %), resulting in ECN lysis and subsequent elimination by the immune system. Additionally, D@T@E-PL pass lysis to release relevant antigens (DNA and flagellin). This antigen promotes the polarization of M2 -type tumor -promoting macrophages towards M1 -type anti -tumor macrophages at the tumor microenvironment by activating Toll -like receptor 4 (TLR4), eliciting immune -mediated anti -tumor responses. The in vivo findings demonstrated that D@T@E-PL intelligent material demonstrated enhanced biosecurity through the lytic circuit and effectively suppressed tumor growth, thereby achieving a dual therapeutic approach combining chemotherapy and immunotherapy for tumor inhibition.