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工程菌介导的唾液酸酶递送重塑肿瘤免疫微环境

中文摘要英文摘要

肿瘤微环境由多种细胞与非细胞成分构成,其影响了肿瘤组织的发生发展与转移,并且阻碍了免疫细胞对肿瘤组织的识别与杀伤。而唾液酸作为一种在多种肿瘤模型中上调的分子,其通过与免疫细胞上的Siglec受体进行结合,进而抑制了免疫细胞的活化。本研究设计了一株以减毒鼠伤寒沙门氏菌ΔppGpp为载体,编码唾液酸酶(nanH)的工程菌SLpnanH。通过质粒构建技术,使用pBAD载体搭载nanH构建工程菌SLpnanH,通过Western Blot实验体外验证,其具有高度的唾液酸酶表达与分泌,同时活性。在体外,通过结晶紫染色与划痕实验,发现其能够对MC38细胞系具有抑制其增殖与迁移的能力。本研究开发的SLpnanH在细菌介导的MC38肿瘤细胞系治疗上有着较好的效果,有着广阔的临床应用前景。

he tumor microenvironment is composed of a variety of cellular and non cellular components, which affect the occurrence, development and metastasis of tumor tissues, and hinder the recognition and killing of tumor tissues by immune cells. Sialic acid, as a molecule upregulated in a variety of tumor models, inhibits the activation of immune cells by binding to siglec receptors on immune cells. In this study, an engineered strain slpnanh encoding sialidase (nanH) was designed with attenuated Salmonella typhimurium ΔppGpp as the carrier. Through plasmid construction technology, the engineered strain slpnanh was constructed using pBAD vector carrying nanH, which has high sialidase activity. In vitro, crystal violet staining and scratch experiments showed that it could inhibit the proliferation and migration of MC38 cell line. The slpnanh developed in this study has a good effect in the treatment of MC38 tumor cell line mediated by bacteria, and has a broad prospect of clinical application.

朱永杰、郑金海

湖南大学生命医学交叉研究院,湖南省长沙市 410013湖南大学生命医学交叉研究院,湖南省长沙市 410013

肿瘤学基础医学生物科学研究方法、生物科学研究技术生物化学分子生物学

分子医学肿瘤微环境唾液酸减毒鼠伤寒沙门氏菌唾液酸酶

Molecular medicineTumor microenvironmentSialic acidAttenuated Salmonella typhimuriumSialidase

朱永杰,郑金海.工程菌介导的唾液酸酶递送重塑肿瘤免疫微环境[EB/OL].(2025-04-25)[2025-06-03].http://www.paper.edu.cn/releasepaper/content/202504-210.点此复制

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