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Updated: May 23, 2025

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基于超分子聚氨酸的纳米疗法可以使癌细胞变硬,以增强T细胞介导的抗癌免疫疗法

Haifen Luo¹, Jingqi Lv¹, Peiye Wen¹

¹Strait Laboratory of Flexible Electronics (SLoFE), Fujian Key Laboratory of Flexible Electronics, Key Laboratory of Opto-Electronic Science and Technology for Medicine of Ministry of Education, College of Photonic and Electronic Engineering, Strait Institute of Flexible Electronics (SIFE, Future Technologies), Fujian Normal University, Fuzhou, Fujian, China.

Nature communications

|March 8, 2025

概括

这项研究引入了新型纳米颗粒,激活STING免疫力,软化瘤,增强T细胞癌症杀伤. 这种方法有效地回归瘤,并在小鼠中产生长期记忆.

科学领域:

免疫学免疫学免疫学
材料科学材料科学材料科学
生物医学工程生物医学工程

背景情况:

激活干扰素基因刺激剂 (STING) 通过启动T细胞反应,显示出癌症免疫治疗的前景.
瘤细胞通过生物力学介导的途径逃避免疫攻击,阻碍T细胞细胞毒性.
克服这些免疫逃避机制对于增强基于STING的癌症疗法至关重要.

研究的目的:

开发一种新的纳米粒子系统,用于结合STING激活和瘤细胞的生物机械调制.
研究增强T细胞反应和克服癌细胞免疫逃避的协同抗瘤效应.
在临床前模型中评估开发系统产生的治疗疗效和长期免疫记忆.

主要方法:

制造基于甲基-β-环极素 (MeβCD) 的高分子聚素 (MSPs) 的氧化还原反应,装载着STING激动剂diaBZI和近红外 (NIR) 探针.
用diABZIs将MSP自组装成纳米粒子 (RDPNs@diABZIs) 进行有针对性的交付.
在雌性瘤携带小鼠模型中对RDPNs@diABZIs的体内评估,评估瘤回归,免疫反应和生存.

主要成果:

在瘤微环境中,RDPNs@diABZIs证明了MeβCD和diABZIs同时释放.
激活的STING启动了新的T细胞反应,而MeβCD则减少了胆固醇,增强了癌细胞的机械性质.
在接受治疗的小鼠中观察到显著的瘤回归,长期免疫记忆和延长生存时间.

结论:

开发的RDPNs@diABZIs有效地将STING通路激活与克服癌细胞生物机械免疫逃避相结合.
这种双重作用的策略导致强大的抗瘤疗效,并建立持久的抗瘤免疫力.
这些发现强调了一种有希望的治疗方法,通过解决免疫激活和瘤物理障碍来增强癌症免疫疗法.

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