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基于聚合物的纳米药物通过免疫抑制瘤微环境的表观遗传重编程来增强声动疗法

Lin Yu¹, Lulu Gao¹, Bing Liang¹

¹Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, PR China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou 225001, PR China.

Journal of controlled release : official journal of the Controlled Release Society

|February 1, 2025

概括

这项研究开发了纳米粒子,将声动疗法与表观遗传重编程相结合,以克服三阴性乳腺癌中免疫抑制性瘤微环境,提高治疗效率和减少转移.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
癌症治疗癌症治疗

背景情况:

声动力疗法 (SDT) 对三阴性乳腺癌 (TNBC) 是有前途的,但受到免疫抑制瘤微环境 (TME) 的限制.
需要有效的策略来克服TME介导的免疫抑制,以提高SDT的疗效.

研究的目的:

开发瘤微环境响应纳米粒子 (GdNPs),封装一个声敏化剂 (Ce6) 和一个表观遗传修饰剂 (Ricolinostat, Ric).
通过重新编程免疫抑制TME来提高TNBC中SDT的有效性.

主要方法:

GdNPs/Ce6-Ric纳米颗粒被设计为通过EPR效应在瘤中积累,并在响应酸性TME时释放载荷.
超声波刺激触发了癌细胞亡和免疫细胞死亡 (ICD) 的ROS生成.
里科林斯塔特的表观遗传调节针对HDAC6/p-STAT3/PD-L1和TGFβ/EMT通路.

主要成果:

GdNPs/Ce6-Ric诱导了ICD,激活了细胞毒性T细胞,增加了NK和细胞毒性T细胞种群,同时减少了Treg细胞.
表观遗传重编程降低了HDAC6 / p-STAT3 / PD-L1通路的调节,协同增强了SDT的抗瘤作用.
通过改善系统性免疫力和抑制TGFβ诱导的上皮-介质细胞转变 (EMT),治疗将肺转移降到最低.

结论:

GdNPs/Ce6-Ric纳米粒子有效地重编程TNBC中的免疫抑制TME.
这种方法协同增强SDT的疗效,为TNBC治疗和转移抑制提供了一个有希望的策略.

关键词:

表观遗传重编程是一种表观遗传重编程.纳米级协调聚合物纳米级协调聚合物声动力学疗法声动力学疗法瘤微环境是一个微环境.

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