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用于瘤免疫治疗的内质网膜向的聚合物-纳米复合体

Haoru Zhu¹, Chang Xu², Yu Geng¹

¹Key Laboratory of Smart Biomaterials of Zhejiang Province and Key Laboratory of Biomass Chemical Engineering of the Ministry of Education of China, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China.

|January 24, 2025

概括

离子 (Mn2+) 通过准内质网膜 (ER) 来激活免疫路径. 针对ER的纳米复合物有效抑制瘤生长,在没有毒性的小鼠中增强生存率.

科学领域:

纳米医学是一种纳米医学.
免疫学免疫学免疫学
癌症治疗癌症治疗

背景情况:

离子 (Mn2+) 是已知的免疫激活剂,增强cGAS和STING蛋白活性.
对于免疫反应至关重要的STING信号传递,主要与内质网膜 (ER) 相关.
将Mn2+向ER可能有助于激活STING通路,从而获得治疗效益.

研究的目的:

设计和评估以为基础的以ER为目标的纳米复合物 (NCs),用于增强STING激活和癌症治疗.
研究这些NCs的生物分布,瘤透和免疫调节效应.
在临床前癌症模型中评估针对ER的Mn2+输送的治疗疗效.

主要方法:

使用Mn2+和一个zwitterionic聚合物 (OPDMA) 合成针对ER的纳米复合物 (Mn/OPDMANCs).
评估NCs的血液循环,瘤积累和转细胞因深度瘤透而发生的变细胞.
评估cGAS-STING通路激活,巨细胞极化和与瘤相关的巨细胞中的IFN-β分泌.
在静脉注射后在小鼠结肠和肝细胞癌模型中对Mn/OPDMANC进行体内测试.

主要成果:

Mn/OPDMA NCs通过吸附介导的转细胞酶表现出长时间的血液循环和有效的深度瘤透.
首选局部化到瘤相关巨细胞的ER,显著提高cGAS-STING通路的激活.
用Mn/OPDMANCs治疗导致巨细胞极化和IFN-β分泌的增强.
在体内研究显示显著的瘤生长减缓 (2.4-5倍) 和延长的生存时间在小鼠与自由2+相比.

结论:

通过Mn/OPDMANCs实现Mn²⁺的ER向输送,可以实现强大的STING激活.
这种策略提供了强大的全身瘤抑制,与自由Mn2+相比,毒性降低.
开发的纳米复合体通过调节瘤免疫微环境,代表了癌症免疫治疗的有希望的方法.

关键词:

cGAS/STING的激活方式癌症免疫治疗癌症免疫治疗纳米复合体是针对内质网膜的纳米复合体.离子是一种离子.金属免疫学 - 金属免疫学

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