双酶驱动的级联反应调节免疫抑制瘤微环境,用于催化疗法和免疫激活
Hengke Liu1, Shanshan Jiang1, Meng Li1
1Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.
ACS nano
|October 21, 2024
概括
这项研究引入了一种双酶平台 (ILH),用于对抗瘤中乳酸驱动的免疫抑制. ILH疗法逆转瘤微环境,激活抗瘤免疫力,并使光声成像指导治疗成为可能.
科学领域:
- 生物医学工程 生物医学工程
- 癌症研究 癌症研究
- 免疫治疗是一种免疫疗法.
背景情况:
- 在瘤微环境 (TME) 中的乳酸积累会产生免疫抑制状态,通过影响瘤相关巨细胞 (TAMs) 来阻碍抗瘤免疫反应.
- 克服乳酸诱导的免疫抑制对于有效的癌症治疗至关重要.
研究的目的:
- 开发一种新的双酶驱动级联反应平台 (ILH),用于调节免疫抑制TME.
- 为了利用这个平台进行光声学 (PA) 成像导向的催化疗法和免疫激活.
主要方法:
- 使用 (Ir) 纳米酶,乳酸氧化酶 (LOx) 和酸 (HA) 构建了ILH平台.
- 研究了Ir纳米酶和LOx消耗乳酸以逆转TME免疫抑制并促进M1TAM两极分化.
- 评估了该平台缓解瘤缺氧,诱导氧化应激,触发免疫细胞死亡 (ICD) 和激活抗瘤免疫力的能力.
- 利用Ir纳米酶的光热特性进行增强的催化和PA信号生成.
- 采用3D多光谱PA成像用于在体内跟踪级联催化疗法过程.
主要成果:
- ILH平台有效地消耗乳酸,将免疫抑制的TME转化为免疫反应的TME.
- 促进了从M2到M1表型的TAM两极化,增强了抗瘤防御.
- 缓解瘤缺氧和诱导氧化应激,导致ICD和激活抗瘤免疫力.
- 证明了平台的PA响应性和成功的体内治疗追踪,使用3D多谱PA成像.
结论:
- 开发的ILH纳米平台为双酶驱动级联催化疗法和免疫激活提供了一种新的策略.
- 这种方法有效调节免疫抑制的TME,为癌症治疗提供了一个有希望的途径.
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