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状纳米组件通过不依赖氧气的枯竭乳酸重塑瘤微环境,以获得有效的光动力免疫疗法

Xuan Zhang¹, Jinwei Bai¹, Shihao Sun¹

¹State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University, Gansu, Lanzhou, 730000, China.

|February 26, 2025

概括

这项研究引入了一种新的纳米组件,可以在不使用氧气的情况下消耗瘤中的乳酸,通过触发免疫细胞死亡和重编程瘤微环境来增强免疫疗法和光动力疗法.

科学领域:

生物医学工程生物医学工程
癌症治疗癌症治疗
免疫学免疫学免疫学

背景情况:

向瘤乳酸代谢是免疫治疗的关键.
目前的乳酸氧化策略加剧瘤缺氧,限制了疗效.
需要一种新的方法来耗尽乳酸而不消耗氧气.

研究的目的:

开发一种针对瘤的纳米组件 (Zn-UCMB) 用于乳酸耗尽.
为了增强光动力学疗法 (PDT) 和免疫疗法通过乳酸耗尽.
研究非依赖氧气的机制及其对瘤微环境 (TME) 的影响.

主要方法:

开发了一种靠近红外光激活的性纳米组件 (Zn-UCMB).
利用TME对选择性乳酸协调和耗尽的反应.
研究了用于增强PDT的H2O2分解为O2.
评估了TME的重编程,包括HIF-1α和VEGF表达.
评估了巨细胞两极分化 (M2到M1) 和瘤抑制.

主要成果:

Zn-UCMB在酸性TME中选择性地耗尽了乳酸.
纳米组件增强了PDT的有效性,并触发了免疫细胞死亡 (ICD).
不依赖氧气的乳酸耗尽重新编程了TME,减少了免疫抑制.
与瘤相关的巨细胞从M2转移到M1表型.
观察到有效抑制瘤生长和转移.

结论:

Zn-UCMB提供了一种新的,不依赖氧气的策略,用于TME中乳酸耗尽.
这种方法克服了现有的乳酸代谢向的局限性.
Zn-UCMB通过诱导ICD和调节TME来增强PDT和免疫疗法.
为癌症治疗和免疫疗法增强提供了有前途的治疗选择.

关键词:

癌症免疫疗法癌症免疫疗法状纳米组件介导免疫细胞死亡.乳酸盐的无氧依赖性耗尽.光动力学疗法是一种光动力学疗法.瘤微环境调制

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