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导向NIR II的可光激活的沉默聚合体促进癌症免疫疗法

Yuquan Zhang¹, Jie Wang¹, Tian Zhang¹

¹School of Life Science, School of Interdisciplinary Science, Aerospace Center Hospital, Key Laboratory of Molecular Medicine and Biotherapy, Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering Beijing Institute of Technology Beijing China.

Exploration (Beijing, China)

|October 30, 2025

概括

这项研究介绍了PTSQ,这是一种用于近红外激活光动力疗法 (PDT) 和siRNA传递的新型聚合物. 将PDT与免疫检查点阻塞相结合,通过增强免疫细胞死亡 (ICD) 和激活抗瘤免疫力,有效治疗瘤.

科学领域:

生物医学工程生物医学工程
癌症研究癌症研究
纳米技术纳米技术

背景情况:

光动力疗法 (PDT) 通过诱导免疫细胞死亡 (ICD) 来增强癌症免疫疗法.
第一代和第二代光敏感剂的局限性包括浅层组织透,阻碍抗瘤功效.
需要先进的光敏剂,具有更好的透和治疗能力.

研究的目的:

开发一种新的近红外 (NIR) 吸收聚合物,PTSQ,用于增强PDT和siRNA传递.
创建PTSQ/siPD-L1复合体,用于联合PDT和免疫检查点阻塞疗法.
评估这种综合方法在临床前癌症模型中的有效性.

主要方法:

合成了一种具有NIR吸收和NIR II光的定制聚合物 (PTSQ).
将PTSQ制成自组装纳米细胞,用于siRNA输送.
开发了PTSQ/siPD-L1复合体,用于联合PDT和PD-L1阻塞.
评估了细胞ICD诱导和PD-L1基因抑制.
在CT26,4T1和患者衍生异种移植 (PDX) 模型中评估了体内抗瘤疗效.

主要成果:

在NIR和NIR II地区,PTSQ证明了有效的PDT和siRNA传递.
PTSQ/siPD-L1复合体有效诱导ICD并抑制PD-L1的表达.
在体内研究表明,在多种癌症模型中显著抑制瘤生长.
治疗激活了免疫细胞,包括T细胞,树突细胞和巨细胞,扭转了瘤微环境.

结论:

与siPD-L1疗法相结合的NIR II引导的PDT为癌症治疗提供了一个有希望的策略.
PTSQ纳米细胞作为 PDT 和基因沉默组合的有效平台.
这种方法通过ICD诱导和免疫细胞激活来增强抗瘤免疫力.

关键词:

根据NIR II指导的光动力学疗法.在PD-L1中.癌症免疫疗法免疫疗法免疫性细胞死亡免疫性细胞死亡小干扰RNARNA的产生.

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