基于洛萨坦的纳米复合液凝通过重塑瘤机械微环境来克服化疗免疫疗法耐药性
Xiaodong Hou1,2,3, Yuting Shen1,2,3, Bin Huang4
1Department of Medical Ultrasound, Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, P.R. China.
Journal of nanobiotechnology
|October 30, 2024
概括
耐化疗瘤具有硬的微环境,阻碍了免疫治疗. 一种新型的凝,提供洛萨坦和氧沙替代这种刚性,增强化疗免疫疗法和减少转移.
科学领域:
- 在瘤学瘤学.
- 生物材料是一种生物材料.
- 免疫治疗是一种免疫疗法.
背景情况:
- PD-1/PD-L1检查点抑制剂显示出有希望的结果,但临床结果往往令人失望,特别是在化学治疗后的耐药瘤中.
- 化疗后的瘤表现出改变的机械特性,包括增加细胞外基质 (ECM) 刚性,这促进了侵略性表型和免疫疗法耐药性.
研究的目的:
- 研究瘤机械微环境 (TMM) 在免疫疗法耐药性的作用.
- 设计一种新的现场水凝系统,用于针对性地输送治疗剂,以重塑TMM并提高化疗-免疫疗法的疗效.
主要方法:
- 开发一个现场纳米复合液凝系统 (LOS&FeOX@Gel) 持续释放洛萨坦 (LOS) 和氧化 (OX).
- 评估水凝通过减少ECM沉积和固体应力来重塑TMM的能力.
- 在临床前模型中评估水凝治疗药物的协同效应与检查点阻断疗法对抗耐火性瘤和转移.
主要成果:
- 该LOS&FeOX@Gel系统有效地提供了LOS和OX,通过减少ECM沉积和固体应力来重塑TMM.
- 持续释放的洛萨坦增强了氧沙的疗效及其相关的免疫效应.
- 基于水凝的方法使化疗后的瘤对检查点阻断疗法的敏感,证明了对癌症转移的协同效应.
结论:
- 调节瘤机械微环境 (TMM) 是克服化疗耐药性和增强免疫治疗的可行策略.
- 开发的水凝系统提供了一个有希望的新辅助疗法,以优化化学免疫疗法对耐火性瘤的好处.
- 这项研究为抗击晚期癌症的"机械免疫工程"方法建立了临床前的理由.
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