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工程纳米粒子启用与瘤相关的巨细胞再极化和细胞复原,用于增强癌症免疫治疗

Yonghua Gong¹, Wenyue Gao¹, Jinyang Zhang¹

¹Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China.

Journal of nanobiotechnology

|June 18, 2024

概括

这项研究介绍了M@SINPs,这是一种纳米粒子系统,可以重新编程免疫抑制性瘤相关巨细胞 (TAMs),以增强癌症免疫疗法. 这种方法增强了巨细胞和抗瘤免疫力,有望改善癌症治疗.

科学领域:

免疫学免疫学免疫学
纳米技术纳米技术
在瘤学瘤学.

背景情况:

与瘤相关的巨细胞 (TAMs) 创造了一个免疫抑制性瘤微环境 (TME).
重振TAM并增强其细胞化对于癌症免疫疗法至关重要但具有挑战性.
目前的策略往往难以同时实现TAM再极化和细胞化.

研究的目的:

开发一个有针对性的纳米粒子系统 (M@SINPs),用于同时提供光敏剂 (IR820) 和SHP2抑制剂 (SHP099).
通过在TME内重塑TAM来加强巨介导癌症免疫疗法.
研究M@SINPs与抗PD-1疗法的协同效应.

主要方法:

为药物输送而构建的TAM向的蛋白纳米粒子 (M@SINPs).
利用激光照射生成M2-TAM到M1-TAM再极化中的活性氧物种 (ROS).
抑制SHP2以阻止CD47-SIRPa通路并恢复M1巨细胞的细胞活性.

主要成果:

M@SINPs成功地联合发射了IR820和SHP099,导致M2-TAM再极化和增强的细胞化.
TAM重塑产生了免疫刺激性TME,促进了内CTL透,抑制了瘤生长.
使用M@SINPs和抗PD-1抗体的组合疗法显示出协同作用的抗癌作用和改善治疗结果.

结论:

M@SINPs通过恢复它们的再极化和细胞功能来有效地重塑TAM.
这种双重行动策略对提高免疫检查点封锁和常规癌症疗法的有效性具有显著的希望.
在癌症治疗中,M@SINPs系统提供了一种新的方法来克服TAM介导的免疫抑制.

关键词:

癌症免疫疗法癌症免疫疗法组合组合是一种组合.纳米颗粒纳米颗粒发细胞症 (phagocytosis) 是一种致死细胞的发生.两极化的偏化与瘤相关的巨细胞.

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