照片触发的工程微生物实现了胃癌的双重表观遗传免疫调节
Chuyun Lou1, Yitong Li2, Ruonan Zhan3
1Department of Radiology, Henan International Joint Laboratory of Medical Imaging, Henan Key Laboratory of Image Diagnosis and Treatment for Digestive System Tumor, Henan Key Laboratory of CT Imaging, The First Affiliated Hospital of Zhengzhou University, No.1, Eastern Jianshe Road, Zhengzhou, 450052, Henan Province, China.
Biomaterials
|August 19, 2025
概括
工程微生物为胃瘤提供DNA甲基化抑制剂,增强癌细胞死亡和免疫反应. 这种新的方法将表观遗传调节与光热疗法结合起来,以提高抗瘤免疫力和预防潜在的转移.
科学领域:
- 表观遗传学和癌症治疗疗法
- 基于微生物组的治疗方法
- 纳米材料在瘤学中的应用
背景情况:
- 异常的DNA甲基化是癌症的标志,通常会使瘤抑制基因沉默.
- 目前的DNMT1抑制剂,如AZA,由于输送和稳定性差,在胃癌中有效性有限.
- 针对瘤微环境 (TME) 对于有效的癌症治疗至关重要.
研究的目的:
- 开发一种由光触发的工程微生物,用于针对性地将DNMT1抑制剂和iMXene输送给胃瘤.
- 通过联合DNA甲基化抑制,光热疗法和免疫系统激活来增强抗瘤功效.
- 研究这种方法在触发免疫细胞死亡和预防转移方面的潜力.
主要方法:
- 使用大肠杆菌将Mo1.33C-AZA和iMXene (Mo1.33C) 输送到TME的工程微生物 (AM@Ec) 的开发.
- 使用808nm近红外 (NIR) 激光照射触发治疗有效载荷并激活光热疗法 (PTT).
- 使用表观基因组和转录基因组分析来评估甲基化变化和免疫通路激活.
主要成果:
- 工程微生物选择性地将Mo1.33C-AZA输送到瘤核心,抑制DNA甲基化并增强抗瘤效应.
- iMXene促进了CT成像和PTT,与表观遗传调节协同,诱导胃癌细胞中的细胞亡和免疫细胞死亡.
- 治疗重塑了TME,促进了树突细胞成熟,激活了全身免疫力,并产生了免疫记忆,显著减少了瘤甲基化和增强了抗瘤免疫反应.
结论:
- 建立了一个创新的诊断和治疗工程微生物平台,用于针对性地提供DNMT1抑制剂和iMXene.
- 结合表观遗传调节和PTT方法有效触发抗瘤免疫力,并显示出治疗固体瘤的潜力.
- 这一策略为瘤学中的表观遗传疗法开辟了新的途径,特别是用于预防癌症转移.
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