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An oral bacterial pyroptosis amplifier against malignant colon cancer
Lou, Xinyu1; Wang, Jinqiang2; Jin, Xiru1; Wang, Xu1; Qin, Bin1; Liu, Dongchun3; Shi, Xianbao4; Ouyang, Defang5; He, Zhonggui1; Sun, Jin1; Li, Hongjun2; Sun, Mengchi6
2024-02-01
Source PublicationNano Today
ISSN1748-0132
Volume54Pages:102091
Abstract

The oncolytic microbe can trigger pyroptotic cancer cell death, but insufficient pyroptotic response of current microbe-based biotherapeutics restricts the antitumor efficiency. Herein, we report an oral bacterial pyroptosis amplifier composed of two bacterial strains, reductive Shewanella oneidensis MR-1 (abbreviated as MR-1) and engineered Escherichia coli (E. coli) with the overexpression of pyranose oxidase, augmenting the pyroptosis effect against colon and metastatic tumors. Each bacterium is camouflaged with hyaluronic acid to survive against the harsh gastrointestinal environment and to enrich in colon tumor sites. Upon the bacteria colonizing at the tumor site, iron sucrose is orally administrated. The following oral administration of Fe(Ⅲ)-contained iron sucrose leads to the intratumoral accumulation of Fe(Ⅱ) by the reduction characteristic of MR-1. Hydrogen peroxide (HO), synthesized by pyranose oxidase from E. coli, serves as the substrate for Fenton reaction to generate toxic hydroxyl radicals through Fe(Ⅱ)-HO-Fe(Ⅲ) recycling between both strains, thereby promoting immunogenic pyroptosis inside the tumor. This can potentiate lymphocyte activation in the gastrointestinal tissues, exerting significant therapeutic efficacy in multiple colon metastatic tumor models. This study offers promising insight into developing future microbe biotherapeutics with enhanced pyroptosis activity in cancer immunotherapy.

KeywordColon And Metastatic Tumors Fe(ⅱ)-h2o2-Fe(ⅲ) Recycling Immunogenic Pyroptosis Microbe Biotherapeutics Oncolytic Microbe
DOI10.1016/j.nantod.2023.102091
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science
WOS SubjectChemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:001135383400001
PublisherELSEVIER SCI LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
Scopus ID2-s2.0-85179439404
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorSun, Jin; Li, Hongjun; Sun, Mengchi
Affiliation1.Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
2.College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, 310058, China
3.School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China
4.Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China
5.Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, China
6.School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110016, China
Recommended Citation
GB/T 7714
Lou, Xinyu,Wang, Jinqiang,Jin, Xiru,et al. An oral bacterial pyroptosis amplifier against malignant colon cancer[J]. Nano Today, 2024, 54, 102091.
APA Lou, Xinyu., Wang, Jinqiang., Jin, Xiru., Wang, Xu., Qin, Bin., Liu, Dongchun., Shi, Xianbao., Ouyang, Defang., He, Zhonggui., Sun, Jin., Li, Hongjun., & Sun, Mengchi (2024). An oral bacterial pyroptosis amplifier against malignant colon cancer. Nano Today, 54, 102091.
MLA Lou, Xinyu,et al."An oral bacterial pyroptosis amplifier against malignant colon cancer".Nano Today 54(2024):102091.
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