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溶酶体中的动态磁力机械力诱导了抗瘤免疫的长期巨细胞再极化

Yingze Li^1,2,3,4, Mengge Zheng⁵, Zhenyan Zhu⁶

¹Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

|February 2, 2026

概括

这项研究引入了一种新的磁力机械方法来触发 lysosomal 膜通透,重编程巨细胞以获得强大的抗瘤免疫力. 这种方法增强了免疫反应,为持久的癌症免疫治疗提供了新的途径.

科学领域:

生物物理学的生物物理.
免疫学免疫学免疫学
纳米技术纳米技术

背景情况:

机械力量越来越多地被认为是免疫细胞功能在抗瘤免疫中的调节者.
由于缺乏精确的工具,了解器官层面的细胞内力量如何影响癌症免疫的机制传导是有限的.

研究的目的:

开发和验证一种新的磁力机械力触发策略,用于诱导细胞内器官水平的力量.
为了研究这种策略在重编程巨细胞以增强抗瘤免疫力中的潜力.

主要方法:

使用自组装磁纳米机器开发磁力机械力触发的溶酶体膜通透化 (MagLMP) 策略.
旋转磁场的应用,通过扭矩诱导的,诱导受控的溶酶体膜损伤.
利用单细胞RNA测序和巨细胞枯竭-重组模型来阐明潜在的分子途径.

主要成果:

该MagLMP策略成功诱导了持续的M1样巨细胞再极化.
鉴定出Galactin 9 (Gal9) 是循环MagLMP的一个关键传感器,激活AMP激活蛋白激酶 (AMPK) 和核因子kappa B (NF-κB) 途径.
这种Gal9-AMPK-NF-κB轴被证实对MagLMP介导的抗瘤作用至关重要.
在用MagLMP策略治疗的肺腺癌小鼠模型中观察到总生存时间的显著延长.

结论:

通过MagLMP进行细胞内机械操纵可以动态调节先天免疫反应.
开发的战略提供了一个有前途的工具,通过利用器官机械传导来实现持久免疫疗法.
这项工作通过精确控制细胞内机械力量,为体内免疫疗法建立了一个新的范式.

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