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工程半导体聚合物纳米激活剂可能激活cGAS-STING通路,并引起长期记忆,防止乳腺癌复发

Haitao Yuan^1,2, Chong Qiu^1,3, Xiaoxian Wang¹

¹Department of Hyperbaric Oxygen Medicine, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518020, P. R. China.

Advanced materials (Deerfield Beach, Fla.)

|December 4, 2024

概括

这项研究引入了一种新的纳米系统,将光热疗法与免疫疗法结合起来,以克服三阴性乳腺癌的抵抗力. 治疗激活STING通路,重编程瘤微环境并增强长期记忆的抗瘤免疫力.

科学领域:

生物医学工程生物医学工程
免疫学免疫学免疫学
材料科学材料科学材料科学

背景情况:

三阴性乳腺癌 (TNBC) 呈现出"冷"的瘤微环境,导致免疫疗法耐药性.
干扰素基因 (STING) 途径激活的刺激器是增强免疫治疗疗效的有希望的策略.
目前的治疗方法在克服TNBC中的免疫抑制方面面临挑战.

研究的目的:

制定一项综合战略,将天生的免疫反应与瘤向光热疗法 (PTT) 结合起来.
重新编程免疫抑制瘤微环境 (TME) 并激活TNBC中的STING通路.
通过克服免疫抵抗来提高免疫疗法的疗效.

主要方法:

使用半导体聚合物纳米激剂 (DPTT-Mn Lipo NPs) 进行PTT.
研究了PTT介导的免疫细胞死亡 (ICD) 诱导和STING通路激活.
评估了TME组件的调制,包括巨细胞极化,T细胞透和树突细胞成熟.
评估了基于DPTT-Mn Lipo NPs的PTT与抗PD-1检查点阻塞疗法的联合治疗.

主要成果:

与DPTT-Mn Lipo NPs一起的PTT有效诱导瘤细胞亡和ICD,重编程TME.
由于ICD释放的dsDNA,免疫细胞 (巨细胞,DCs) 中确认了STING通路的激活.
观察到M1巨细胞极化,T细胞透率增加,DC成熟和I型干扰素分泌.
在与抗PD-1疗法相结合时,已证明有效的瘤抑制和重要的是长期免疫记忆.

结论:

开发的纳米系统通过STING通路调制有效地激活抗瘤免疫力.
这种方法可以重新编程免疫抑制的TME,并提高TNBC的免疫疗法疗效.
组合疗法显示出瘤根除和建立长期免疫记忆的潜力,防止复发.

关键词:

cGAS-STING 的使用情况.引起长期记忆的产生.免疫性细胞死亡免疫性细胞死亡光热疗法是一种光热疗法.半导体聚合物纳米激励剂半导体聚合物纳米激励剂

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