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微RNA诱导的瘤相关巨细胞的重编程,以调节瘤免疫微环境

Yina Wu¹, Jinwon Park¹, Enzhen Xu¹

¹College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Journal of controlled release : official journal of the Controlled Release Society

|March 2, 2025

概括

用抗SIRPα抗体修饰的纳米颗粒向与瘤相关的巨细胞 (TAM),将microRNA-155 (miR155@aSIRPα-LNP) 输送重编程的TAM到抗瘤表型,增强癌症免疫疗法.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
纳米医学是一种纳米医学.

背景情况:

瘤相关巨细胞 (TAMs) 在瘤微环境中普遍存在,并且经常促进瘤生长.
TAMs表达信号调节蛋白α (SIRPα),该蛋白与CD47结合于瘤细胞,抑制了细胞分裂.
目前的免疫疗法在治疗冷固体瘤方面面临挑战,原因是免疫抑制瘤微环境.

研究的目的:

开发一个针对microRNA-155 (miR155) 到TAMs的纳米粒子传递系统.
将TAM重新编程为抗瘤表型,并增强抗癌免疫力.
研究这种方法在克服目前固体瘤免疫疗法的局限性方面的潜力.

主要方法:

脂质纳米颗粒是用抗SIRPα抗体 (aSIRPα) 设计的,用于针对性地传递miR155 (miR155@aSIRPα-LNP).
评估了纳米粒子吸收和与TAM和B16F10黑色素瘤细胞的相互作用.
在黑色素瘤小鼠模型中评估了miR155@aSIRPα-LNP对TAM表型,细胞和瘤微环境的影响.

主要成果:

该aSIRPα修改确保了TAM的纳米颗粒的向吸收,而不是瘤细胞.
这些纳米颗粒破坏了SIRPα-CD47相互作用,阻断了抗细胞酶信号.
miR155@aSIRPα-LNP治疗将TAM重编程为一种抗瘤表型,增加细胞化并释放抗瘤细胞因子.
这种瘤微环境的重塑导致细胞毒性T细胞透率增加和调节性T细胞减少,抑制瘤的进展.

结论:

用miR155装载纳米颗粒准TAM上的SIRPα是一种可行的策略,可以调节免疫抑制瘤微环境.
这种方法增强了巨细胞介导的抗瘤活性,并促进了T细胞介导的免疫力.
miR155@aSIRPα-LNP代表了一种有前途的治疗策略,用于增强癌症免疫疗法,特别是冷固体瘤.

关键词:

脂质纳米颗粒是一种纳米粒子.这是一个微型RNA.重编程重编程是一种重编程.瘤微环境是一个微环境.与瘤相关的巨细胞.

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