工程细菌外膜囊泡协同促进通过持续的DNA损伤通过放射治疗诱导的超活性抗瘤免疫力
Guangyu Ju1, Xiao Liu2, Hongcang Gu2
1Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, PR China; Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, PR China.
Biomaterials advances
|February 21, 2026
概括
这项研究引入了一种新型纳米系统,通过放大DNA损伤和抑制DNA损伤反应 (DDR) 来增强放射治疗的抗瘤作用. 这种方法可以增强抗瘤免疫力,并减少瘤的放射电阻,从而改善治疗结果.
科学领域:
- 在瘤学瘤学.
- 纳米技术纳米技术
- 免疫学 免疫学 免疫学
背景情况:
- 放射治疗诱导DNA损伤,激活抗瘤免疫的cGAS-STING通路.
- 然而,DNA损伤反应 (DDR) 可以抑制这一关键的炎症反应.
- 克服DDR介导的抑制是提高放射治疗疗效的关键.
研究的目的:
- 开发一种纳米系统,可以放大DNA损伤并抑制DDR,从而增强抗瘤免疫力.
- 为了改善瘤透和治疗剂的输送.
- 为了协同地将纳米粒子介导的损伤与免疫激活相结合.
主要方法:
- 工程外膜囊泡 (OMVs) 使用iRGD用于瘤定位.
- 装载有磁铁纳米颗粒 (Fe3O4 NPs) 和ATR抑制剂 (VE822) 的OMV.
- 使用Fe3O4NP用于芬顿反应和VE822用于ATR抑制,以放大DNA损伤并阻止DDR.
主要成果:
- 实现了深度瘤透和血脑屏障的穿越.
- 通过协同Fe3O4NP和ATR抑制,持续的DNA损伤和抑制DDR.
- OMVs激活了天生的免疫力,增强了整体抗瘤免疫反应.
- 在小鼠中表现出显著的瘤生长抑制.
结论:
- 开发的纳米系统有效地放大DNA损伤并抑制DDR,增强放射治疗的抗瘤作用.
- 这种策略克服了瘤的放射电阻,并促进了T细胞透.
- 这种方法为增强抗瘤免疫力和改善癌症治疗提供了一种有希望的方法.
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