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中性细胞劫持囊泡通过放射治疗后的向siRNA输送抑制NET介导的转移

Hongmei Cao¹, Jiayu Mi¹, Shuxiang Wang¹

¹State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Tianjin Institutes of Health Science, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China.

Journal of controlled release : official journal of the Controlled Release Society

|January 16, 2026

概括

放射治疗可以促进癌症的传播. 一个新的纳米平台劫持中性粒细胞来提供基因沉默疗法,重新编程它们来对抗瘤并抑制转移.

科学领域:

在瘤学瘤学.
纳米医学是一种纳米医学.
免疫治疗是一种免疫疗法.

背景情况:

放射治疗 (RT) 矛盾的是,通过炎症和中性粒细胞外细胞陷 (NETs) 来增强瘤转移.
瘤细胞上的DNA传感器CCDC25通过识别NET和促进细胞骨重塑来调解NET驱动的转移.

研究的目的:

开发一个中性粒细胞劫持纳米平台 (OS-D) 用于针对性地传递CCDC25 siRNA.
将中性粒细胞重新编程为抗瘤表型,并抑制RT诱导的转移.

主要方法:

使用细菌外膜囊泡 (OMV) 构建的OS-D纳米平台封装了CCD25siRNA.
用pH敏感的DSPE-PEOz修改的OMV用于瘤响应释放.
OS-D利用病原体关联分子模式 (PAMP) 进行选择性中性粒细胞结合和RT诱导的招募以进行向性传递.

主要成果:

带有OS-D的中性粒细胞在瘤部位积聚,输送siRNA使瘤细胞中的CCDC25沉默.
破坏NET介导的转移信号和抑制转移.
活性中性粒细胞分泌细胞毒性和免疫刺激因子,增强抗瘤免疫力.

结论:

通过将基因沉默与免疫调节相结合,OS-D纳米平台有效地抑制RT诱导的转移.
该策略提供了一种安全和可翻译的方法,以提高RT的疗效并克服瘤的进展.

关键词:

美国疾病预防控制和预防中心CCDC25 工程设计的细菌囊泡.中性粒细胞外细胞陷 (NETs)通过中性粒细胞介导的分娩.辐射疗法辐射疗法瘤转移的发生.

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