共生
前药
共轭体系
靶向治疗
癌症治疗
癌症研究
癌症
医学
生物
化学
内科学
药理学
遗传学
细菌
有机化学
聚合物
作者
Haosheng Shen,Changyu Zhang,Shengjie Li,Yuanmei Liang,Li Ting Lee,Nikhil Aggarwal,K.S. Wun,Fei Liu,Saravanan Prabhu Nadarajan,Cheng Weng,Hua Ling,Joshua K. Tay,De Yun Wang,Shao Q. Yao,In Young Hwang,Yung Seng Lee,Matthew Wook Chang
标识
DOI:10.1038/s41467-024-48661-y
摘要
Abstract Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%.
科研通智能强力驱动
Strongly Powered by AbleSci AI