可光切换的动态和RNAi协同剂与定制接口和受控释放重编程瘤免疫抑制利基
Hongjie Xiong1, Zhongquan Song2, Tingya Wang3
1State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China.
Biomaterials
|August 4, 2024
概括
一种新的可光激活疗法 (Apt-LPR) 通过重新编程瘤微环境来增强三阴性乳腺癌的免疫疗法. 这种方法结合了光动力学疗法 (PDT) 和RNA干扰 (RNAi) 来增强全身抗瘤免疫力.
科学领域:
- 生物医学工程 生物医学工程
- 癌症研究 癌症研究
- 免疫治疗是一种免疫疗法.
背景情况:
- 三阴性乳腺癌 (TNBC) 由于其免疫抑制瘤微环境 (ITM) 具有挑战性.
- 目前的免疫疗法在克服这种ITM方面面临局限性.
- 开发新的策略来增强瘤内的免疫细胞活性至关重要.
研究的目的:
- 开发一种可光激活的免疫协同增强剂,Apt-LPR,用于TNBC免疫治疗.
- 研究Apt-LPR在ITM重编程中的机制.
- 在临床前模型中评估Apt-LPR的治疗疗效.
主要方法:
- 通过将miR-34a和光敏感剂与瘤特异性瘤体一起加载到脂质体中来构建Apt-LPR.
- 研究了胺体 - 脂质体 - 目标细胞接口机制.
- 评估Apt-LPR诱导亡,降低PD-L1调节,并在近红外辐射时激活免疫细胞的能力.
- 在4T1异种移植小鼠和MDA-MB-231异种移植斑马鱼模型中进行评估.
主要成果:
- 阿普特-LPR在目标结合时展示了一个独特的"站立"的阿普特胺接口,中和脂质体潜力并增强稳定性.
- 光激活的Apt-LPR触发了miR-34a的逐步溶酶体逃逸,诱导瘤细胞亡和PD-L1下调.
- 该疗法有效地释放了与瘤相关的抗原,将ITM转化为"免疫热"环境.
- Apt-LPR抑制了初级和远端瘤的生长,减少了小鼠的肺转移,并在斑马鱼中显示了光控制释放和向.
结论:
- Apt-LPR是一种可光开关的光动力学疗法/RNAi免疫刺激器.
- 这种方法有效地重新编程免疫抑制瘤微环境.
- Apt-LPR提供了一种有前途的策略,以提高癌症免疫疗法的疗效,特别是TNBC.
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