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生物响应和免疫治疗纳米材料重塑瘤微环境,以加强免疫检查点封锁

Tianxu Fang^1,2, Xiaona Cao^1,2, Li Wang^1,2

¹Department of Biomedical Engineering, McGill University, Montreal, QC, H3G 0B1, Canada.

Bioactive materials

|November 29, 2023

概括

这项研究开发了带有触酶的碳酸纳米颗粒 (CAT@CaCO3 NPs) 来重塑瘤微环境 (TME). 这种方法可以增强抗瘤免疫力,并提高免疫检查点阻塞治疗癌症治疗的疗效.

科学领域:

生物医学工程生物医学工程
癌症免疫学癌症免疫学
纳米医学是一种纳米医学.

背景情况:

免疫检查点阻塞 (ICB) 疗法对癌症治疗有希望,但由于免疫抑制瘤微环境 (TME) 而面临局限性.
特征为酸性,缺氧和活性氧物种 (ROS) 的TME损害了抗瘤免疫细胞的功能.
开发重编程TME的策略对于提高癌症免疫疗法疗效至关重要.

研究的目的:

开发适应TME的,加载着catalase的碳酸纳米颗粒 (CAT@CaCO3NP) 用于多模式的TME重塑.
研究CAT@CaCO3NP在增强抗瘤免疫反应和ICB治疗疗效方面的潜力.

主要方法:

制造带有甲基酶的碳酸纳米颗粒 (CAT@CaCO3NP).
评估纳米粒子介导的TME调制 (pH正常化,ROS清理,O2生成).
评估免疫细胞激活,巨细胞两极分化和与抗PD-1疗法结合的抗瘤免疫反应.

主要成果:

CAT@CaCO3 NPs有效地使酸性TME正常化,清除ROS,并产生O2.
纳米颗粒治疗促进了M1巨细胞的两极分化,并增强了瘤抗原的呈现.
通过激活T细胞介导免疫,CAT@CaCO3NP和抗PD-1的联合治疗显著抑制了瘤生长和远程转移.

结论:

CAT@CaCO3NP作为TME重塑和免疫治疗的多功能平台.
当地的CAT@CaCO3NP与抗PD-1治疗相结合的管理可以引起强大的本地和全身抗瘤免疫反应.
这种组合策略有望克服TME介导的抗癌免疫疗法的阻力.

关键词:

碳酸纳米颗粒的碳酸.癌症免疫疗法癌症免疫疗法药物交付是药物交付的过程.免疫检查点抑制剂免疫检查点抑制剂免疫调节免疫调节瘤微环境是一个微环境.

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