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多功能纳米酶用于通过非激活PI3K/AKT信号通路来进行声动力增强免疫检查点阻塞疗法

Mei Wen¹, Pu Qiu¹, Jialan Meng²

¹State Key Laboratory of Advanced Fiber Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.

|February 2, 2025

概括

新的纳米酶通过禁用PI3K/AKT通路来增强癌症免疫疗法,促进T细胞反应并减少瘤生长. 这种方法显示出克服瘤免疫抑制和预防转移的希望.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

癌症免疫疗法因T细胞激活不足和免疫抑制瘤微环境而面临挑战.
针对PI3K/AKT等关键信号通路对于增强抗瘤免疫反应至关重要.

研究的目的:

开发pH选择性的多酶模拟纳米酶用于瘤声免疫疗法.
通过使用Pd-hemoporfin (Pd⁰/Pd²⁺‒H) 纳米剂来研究PI3K/AKT通路的失活.
评估纳米酶和抗PD-L1治疗在控制瘤生长和转移方面的联合疗效.

主要方法:

合成Pd-hemoporfin (Pd⁰/Pd²⁺‒H) 纳米剂具有catalase-mimetic, peroxidase-mimetic和sonodynamic的属性. 这种纳米剂的合成过程中使用了Pd-hemoporfin,Pd⁰/Pd²⁺‒H,Pd²⁺,Pd³,Pd⁴,Pd⁵,Pd⁶,Pd⁷,Pd⁸,Pd⁹,Pd¹⁰,Pd¹⁰,Pd¹⁰,Pd¹,Pd¹,Pd^,Pd¹,Pd
评估纳米剂诱导的O2生成和反应性氧物种 (ROS) 的升高.
在基因和蛋白质水平上对PI3K/AKT通路抑制的评估.
免疫细胞死亡,树突细胞招募和T细胞激活的分析.
在体内研究将纳米剂与抗PD-L1疗法结合起来,以评估瘤生长抑制和转移预防.

主要成果:

Pd⁰/Pd²⁺‒H纳米剂成功地创造了富含氧气的环境并增加了ROS水平.
增加的ROS下调PI3K和p-AKT表达,导致PI3K/AKT通路的失活.
观察到增强的免疫细胞死亡,促进树突细胞招募和T细胞激活.
使用Pd0/Pd2+‒H和抗PD-L1的联合治疗显著抑制了原发性瘤的生长,并预防了转移.

结论:

具有pH选择性的多酶模拟纳米酶通过向PI3K/AKT通路,有效地促进子免疫疗法.
这种策略增强了抗瘤免疫力,并为癌症治疗提供了潜在的治疗方法.
这些发现为利用纳米酶进行信号通路调节和开发新型抗瘤策略提供了洞察力.

关键词:

免疫治疗是一种免疫疗法.金属有机框架的框架.纳米酶纳米酶是一种纳米酶.通过PI3K/AKT路径.声疗法声疗法声疗法

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