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宏细胞中RNAi的高效聚合物纳米颗粒揭示了STAT3/STAT6被击倒后对极化标记物的复杂影响

Maximilian Walther¹, Robert Jenke¹, Achim Aigner¹

¹Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Leipzig University, Faculty of Medicine, Leipzig, Germany.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

|February 23, 2024

概括

将瘤相关巨细胞 (TAM) 从M2重编程到M1是一种有前途的癌症免疫疗法. 氨酸修饰的纳米颗粒有效地将siRNA传递给巨细胞,从而使STAT6倒退并增强抗瘤活性.

科学领域:

免疫学免疫学免疫学
纳米技术纳米技术
癌症治疗癌症治疗

背景情况:

瘤相关巨细胞 (TAMs) 是影响瘤进展和治疗反应的关键免疫细胞.
TAM存在不同的激活状态 (M1:抗瘤,M2:亲瘤).
将M2 TAM重聚到M1是一种潜在的免疫疗法策略.

研究的目的:

评估纳米粒子系统,以有效地向巨细胞传递siRNA.
为了调查siRNA介导的基因敲除TAM再极化.
评估复极化对抗瘤活性的影响.

主要方法:

对基于PEI和PPI的纳米颗粒进行了测试,用于在巨细胞中传递siRNA.
使用氨酸修饰的纳米粒子 (LP10Y,P5Y,PPI-Y) 进行基因淘汰.
分析了M2/M1标记物变化和STAT6/STAT3倒置效应.
在共同培养模型中评估瘤细胞化.

主要成果:

用氨酸修饰的PEI和PPI纳米颗粒在巨细胞的基因淘汰中表现出高效率.
STAT6或STAT3倒置诱导的M2到M1再极化.
通过PPI-Y/siRNA增强瘤细胞的巨细胞细胞酶.
确定了STAT3和STAT6在巨细胞再极化中的非冗余作用.

结论:

特定的氨酸修饰PEI/PPI纳米颗粒对巨细胞转染是有效的.
通过siRNA介导的STAT6淘汰是TAM再极化的一个有前途的方法.
再极化巨细胞表现出增强的瘤细胞抑制功能.

关键词:

聚乙烯胺 (PEI) 是一种巨细胞是一个巨细胞.聚烯胺 (PPI) 是一种的 siRNA 转染.氨酸修饰的PEI/PPI是一种PEI.

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