细胞内动态超分子聚合以引起瘤热亡
Qihui Wang1, Jingtao Zheng1, Lei Rong2
1Center for Molecular Metabolism, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing 210094, China.
Journal of the American Chemical Society
|March 4, 2026
概括
这项研究引入了一种新的动态超分子聚合系统,使用脱氧氨酸 (dG) 和聚乙烯糖醇 (PEG) 来控制细胞命运. 该系统对离子 (K+) 水平作出反应,使得向癌症治疗和免疫细胞死亡成为可能.
科学领域:
- 生物材料科学 生物材料科学
- 聚合物化学 聚合物化学
- 纳米技术 纳米技术
背景情况:
- 超分子聚合提供了指导细胞命运的潜力,但目前的系统往往是不可逆转的,容易降解.
- 现有的基于或核酸的单体由于酶的不稳定性而面临限制.
- 对于先进的生物材料应用,需要动态,稳定和响应的系统.
研究的目的:
- 开发一种动态的超分子聚合系统,基于一种用于控制细胞命运调节的新型共聚物.
- 为了研究由离子 (K+) 水平触发的聚合机制.
- 通过诱导免疫细胞死亡和增强抗瘤功效来评估该系统在癌症治疗中的潜力.
主要方法:
- 合成了一种共聚合物 (poly ((deoxyguanosine-co-poly ((ethylene glycol) 甲基烯酸盐) (poly ((dG-co-PEG-MA)) 与酶稳定的dG和PEG吊.
- 标志着共聚物在水溶液中的自我组装,形成dG-宏体 (纳米立方体).
- 研究了K+触发的超分子聚合成纤维和交联网,以及其动态,非循环性质.
主要成果:
- 该dG-宏体在水中自组装成纳米立方体,使用PEG吊促进3D扩展.
- 暴露于高K+水平,启动了dG-宏体的动态,非循环聚合成更高阶结构.
- 在体内研究显示了循环中的惰性,增强瘤积累,内部化后K + 枯竭,以及激活热,导致免疫细胞死亡.
- 与抗PD-L1疗法的协同作用显著增强了CD8+ T细胞反应和抗瘤疗效.
结论:
- 开发了一种新的动态,非循环的超分子聚合系统,能够响应逐步的K+增加.
- 通过诱导免疫细胞死亡和增强免疫疗法,证明了该系统在向癌症治疗中的潜力.
- 扩大了化学工具包,用于创建调节细胞命运的先进生物材料.
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