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利用工程益生菌实现缺氧肿瘤放射增敏。

Hypoxic Tumor Radiosensitization Using Engineered Probiotics.

机构信息

Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, Hubei, 430072, China.

出版信息

Adv Healthc Mater. 2021 May;10(10):e2002207. doi: 10.1002/adhm.202002207. Epub 2021 Feb 28.

DOI:10.1002/adhm.202002207
PMID:33645010
Abstract

Owing to their ability to rapidly proliferate in specific niches and their amenability to genetic manipulation, bacteria are frequently studied as potential diagnostic or therapeutic bioagents in a range of pathological contexts. A sustained oxygen supply within solid tumors is essential in order to achieve positive radiotherapy (RT) outcomes, as these intratumoral oxygen levels are necessary to facilitate RT-induced reactive oxygen species (ROS) generation. In this study, a genetically engineered variant of the tumor-targeting probiotic E. coli Nissle 1917 bacteria that secret catalase is utilized to alleviate intratumoral hypoxia and to thereby enhance tumor radiosensitivity. These engineered bacteria are able to facilitate robust O evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo, significantly inhibiting tumor growth. Overall, the study highlights a novel and practical approach to enhance the efficacy of tumor RT, underscoring the value of future research in the field of probiotic medicine.

摘要

由于其在特定小生境中快速增殖的能力及其易于遗传操作的特点,细菌经常被研究作为潜在的诊断或治疗生物制剂,用于多种病理情况。在实体肿瘤中持续供氧对于实现积极的放射治疗(RT)结果至关重要,因为这些肿瘤内的氧水平对于促进 RT 诱导的活性氧(ROS)的产生是必要的。在这项研究中,利用一种基因工程改造的肿瘤靶向益生菌大肠杆菌 Nissle 1917 的变体,该变体细菌能够分泌过氧化氢酶,以减轻肿瘤内缺氧,并由此增强肿瘤对放射治疗的敏感性。这些工程化的细菌能够在体外和体内对 X 射线照射做出反应,促进大量 O2 的产生和随后的 ROS 的产生,从而显著抑制肿瘤生长。总的来说,这项研究强调了一种增强肿瘤 RT 疗效的新的实用方法,突出了益生菌医学领域未来研究的价值。

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Resynthesis of synthetic biology techniques: combining engineered bacteria with other antitumour therapies.合成生物学技术的再合成:将工程菌与其他抗肿瘤疗法相结合。
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Ultrasound-responsive engineered bacteria mediated specific controlled expression of catalase and efficient radiotherapy.超声响应性工程菌介导过氧化氢酶的特异性可控表达及高效放射治疗。
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