工程纳米敏化剂重塑TME用于低免疫性"冷"和"热"瘤转化
Zhongqing Liu1,2,3, Ziqi Wang4,1,2, Zhishuai Zhang4,1,2
1NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin 150001, People's Republic of China.
Nano letters
|January 29, 2024
概括
这项研究引入了一种对超声响应的纳米敏感剂,以克服瘤免疫抑制并增强癌症免疫治疗. 将这种纳米敏感剂与α-PD-L1疗法相结合,通过重塑瘤微环境,显著增强了抗瘤效应.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 免疫治疗是一种免疫疗法.
背景情况:
- 阿尔法-PD-L1疗法对癌症治疗有希望,但受到密集的细胞外基质 (ECM) 和瘤免疫抑制微环境 (TIME) 的限制.
- 克服时间障碍对于提高癌症免疫疗法的疗效至关重要.
研究的目的:
- 设计一种超声响应的纳米敏感剂 (URNS),用于输送洛萨坦 (LST) 和聚乙烯胺 (PEI).
- 为了重塑TIME,将"冷"瘤转化为"热"瘤,并提高对α-PD-L1疗法的敏感性.
主要方法:
- 一种对超声响应的纳米敏感剂 (URNS) 设计用于封装LST和PEI.
- 使用非侵入性超声波触发ROS生成,导致URNS解离,并在瘤部位释放LST和PEI.
- URNS和alpha-PD-L1的联合疗法在体内对其抗瘤疗效进行了评估.
主要成果:
- 设计的URNS有效地传递了LST和PEI,重塑了TIME,并促进了"冷"到"热"的瘤转变.
- 结合URNS和α-PD-L1疗法,在体内实现了90%的瘤抑制率.
- 与单独的α-PD-L1治疗相比,这种组合治疗的抑制率高出1.7倍.
结论:
- 通过重塑瘤微环境,URNS显著提高了α-PD-L1疗法的疗效.
- 这种方法为优化癌症免疫疗法和克服治疗耐药性提供了一个有希望的策略.
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