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瘤微环境激活Cu交叉连接近红外声敏化器用于可视化cuproptosis增强的声动力癌症免疫疗法

Jinyan Hu¹, Lang Yan¹, Zhi Cao²

¹Department of Health Toxicology, College of Naval Medicine, Naval Medical University, Shanghai, 200433, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|September 27, 2024

概括

这项研究引入了Cu-IR783纳米粒子用于向声动疗 (SDT). 这些纳米粒子在瘤中选择性地激活,增强活性氧物种 (ROS) 生成,并触发细胞死亡,以有效治疗癌症.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
在瘤学瘤学.

背景情况:

声动力疗法 (SDT) 显示出由于高组织透率的深层瘤的前景.
目前的SDT面临的挑战是,sonosensitizer在正常组织中的积累,导致非目标效应.
开发有针对性的疗法平台对于有效和安全的局部瘤治疗至关重要.

研究的目的:

开发一个智能治疗学平台,Cu-IR783纳米粒子 (NP),用于选择性激活和可视化在位声动力学疗法 (SDT).
为了研究SDT,化学动力学疗法 (CDT) 和cuproptosis的联合治疗效果.
探索免疫抑制瘤微环境 (TME) 的逆转和诱导全身抗瘤免疫.

主要方法:

制造具有瘤微环境 (TME) 响应协调键的Cu-IR783纳米粒子.
使用 TME 触发 IR783 的选择性激活,以可视化 in situ SDT.
研究Cu+介导的顿类反应,用于反应性氧物种 (ROS) 放大.
通过DLAT寡合化和线粒体功能障碍分析Cu+诱导的cuproptosis.
评估免疫抑制TME的逆转和诱导免疫细胞死亡.

主要成果:

Cu-IR783 NPs在TME中表现出选择性激活,使得在现场可视化SDT.
瘤特异性释放的Cu离子导致ROS的级联放大,并触发了cuproptosis.
提高ROS水平和cuproptosis可以逆转免疫抑制的TME.
疗效平台诱导免疫细胞死亡,促进强大的系统性免疫反应对抗初级和远程瘤.

结论:

开发的Cu-IR783NP为针对性抗瘤治疗提供了一个新的策略.
以受控的方式将SDT,CDT和cuproptosis整合在一起,为可视化局部癌症治疗提供了一种强大的方法.
这项工作为克服当前SDT的局限性和增强抗瘤免疫力提供了一个独特的范式.

关键词:

这就是cuproptosis.免疫疗法免疫疗法智能纳米组件智能纳米组件瘤特异性的拆解方法视觉化的声动力学治疗.

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