有效的TNBC免疫疗法通过双重重编程透瘤的树突细胞和瘤相关的巨细胞与刺激响应的miR155纳米复合体
Zhenghui Jing1, Yanfeng Li1, Jinxiao Song1
1School of Basic Medicine, Qingdao Medical College, Qingdao University, PR China.
International journal of biological macromolecules
|September 18, 2023
概括
这项研究开发了pH / ROS响应的microRNA-155纳米复合体,用于重新编程瘤透的树突细胞和瘤相关的巨细胞,增强小鼠三阴性乳腺癌 (TNBC) 的免疫疗法.
科学领域:
- 生物医学工程 生物医学工程
- 癌症免疫学 癌症免疫学
- 纳米医学是一种纳米医学.
背景情况:
- 三重阴性乳腺癌 (TNBC) 由于高死亡率和预后不佳而构成重大挑战.
- 在瘤微环境中的瘤透树突细胞 (TIDC) 和瘤相关巨细胞 (TAM) 关键调节免疫反应.
- 克服TIDC和TAM的免疫抑制功能对于有效的癌症免疫疗法至关重要.
研究的目的:
- 开发适应pH/ROS的微RNA-155 (miR155) 纳米复合体 (MiR@PCPmP NP) 用于重编程TIDC和TAM.
- 通过调节瘤免疫微环境来增强三阴性乳腺癌 (TNBC) 免疫疗法.
- 在临床前TNBC模型中评估开发的纳米平台的治疗疗效和安全性.
主要方法:
- 用miR155.5自组装的pH/ROS可裂解共聚合物纳米粒子 (PEG-CDM-PEI[Man]-ox-PCL) 的制造.
- 通过曼诺酶受体向,证明TIDC和TAM通过选择性吸收纳米复合物.
- 评估纳米颗粒介导的内分体逃逸,miR155释放,以及随后的免疫细胞在体外和体内重新编程.
- 对4T1瘤携带小鼠的抗瘤疗效,免疫细胞透 (CD8+ T细胞) 和转移抑制的评估.
主要成果:
- MiR@PCPmP NPs表现出TIDCs和TAMs选择性的细胞吸收,随后是高效的内体逃生和miR155释放.
- 纳米复合体有效地重新编程TIDC和TAM,将免疫微环境转移到抗瘤状态.
- 观察到抗瘤免疫反应的显著改善,其特征是CD8+ T细胞透率增加和免疫抑制成分的抑制.
- 这些纳米颗粒显示出强大的抑制原发性瘤和肺转移,没有明显的系统毒性.
结论:
- 使用miR155纳米复合体对TIDC和TAM进行双重重编程,代表了TNBC免疫疗法的有前途战略.
- 开发的纳米平台显示了通过调节瘤免疫微环境来治疗TNBC的潜力.
- 这种方法可能适用于具有类似免疫抑制瘤微环境的其他癌症.
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