三特性的分子印记 lysosomal 纳米降解剂使细胞因子风暴的协同治疗成为可能
Jingran Chen1, Weihua Lu1, Ying Li1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University 163 Xianlin Avenue Nanjing 210023 China zhenliu@nju.edu.cn.
Chemical science
|October 2, 2025
概括
我们开发了一种新的三特异分子印制聚合物 (tsMIP) 纳米降解器,用于同时向降解IL-6和TNF-α. 这种方法为细胞因子释放综合征的协同抗炎疗法提供了一个有希望的策略.
科学领域:
- 生物材料科学 生物材料科学
- 免疫学 免疫学 免疫学
- 纳米技术纳米技术
背景情况:
- 细胞因子释放综合征 (CRS) 或细胞因子风暴是由IL-6和TNF-α等过度的炎症性细胞因子驱动的.
- 目前的向性细胞因子降解策略在模块化,成本,复杂性和基质范围方面面临挑战.
- 对CRS的有效早期干预需要新的治疗方法.
研究的目的:
- 开发一种基于分子印记聚合物 (tsMIP) 的三特异性 lysosome-targeted 嵌合体,用于同时降解IL-6和TNF-α.
- 评估tsMIP在细胞因子风暴的协同抗炎治疗中的治疗潜力.
- 为了证明tsMIP的可行性作为一种用于炎症疾病的多功能纳米降解剂.
主要方法:
- 合成了tsMIP,使用IGF2R,IL-6和TNF-α的非类表位作为高亲缘关系结合的模板.
- 设计的tsMIP捕获IL-6和TNF-α,在细胞表面准IGF2R,并促进 lysosomal降解.
- 利用急性肺损伤小鼠模型来评估通过鼻内给药的in vivo抗炎疗效.
主要成果:
- tsMIP显示了对IL-6,TNF-α和IGF2R的高亲和力结合.
- 用tsMIP治疗显著降低了IL-6,TNF-α和下游信号蛋白的水平 (p-STAT3,p-NF-κB p65).
- 在活体研究中,在急性肺损伤小鼠模型中显示出强大的炎症缓解,证实了有效的CRS治疗.
结论:
- 开发了一种三特性的分子印记 lysosomal 纳米降解剂 (tsMIP) 用于协同抗炎作用.
- tsMIP有效降解点细胞因子,并阻断下游的炎症信号通路.
- 这种多功能纳米降解器策略显示出治疗细胞因子风暴和其他炎症状况的巨大潜力.
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