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一种I型光敏剂-聚合物通过强迫H聚合来增强SING免疫疗法来增强反应性氧物种的产生

Zhixiong Wang¹, Wen Ma², Zhen Yang²

¹Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.

Journal of the American Chemical Society

|October 9, 2024

概括

这项研究开发了一种新型纳米激动剂,将STING激动剂与光敏剂结合起来,以增强癌症免疫疗法. 这种方法有效地根除了瘤,并通过增强免疫细胞活动改善了长期存活.

科学领域:

免疫学
材料科学
癌症学

背景情况:

干扰素基因刺激 (STING) 途径对于抗瘤免疫至关重要.
在癌症治疗中,对STING激动剂的全身传递和对单一治疗的耐药性是重大挑战.
目前的STING疗法减少了自然杀手细胞的增殖.

研究的目的:

开发一种用于增强STING免疫疗法的新型纳米激活剂.
克服系统性STING激动剂和耐药性的挑战.
改善NK细胞增殖和细胞毒性T淋巴细胞的反应.

主要方法:

在含有I型光敏感剂 (NBS) 的聚合体内封装STING激活剂 (diABZI),以产生PNBS/diABZI.
使用NBS的H聚合和系统间交叉来放大反应性氧物种 (ROS) 的产生.
在小鼠模型中通过静脉注射系统注射PNBS/ diABZI.

主要成果:

PNBS/diABZI证明了增强的超氧离子和单片氧生成.
光动力疗法损害了缺氧瘤细胞,并刺激了NK和细胞毒性T淋巴细胞的增殖.
单次使用消除了正位乳腺瘤,建立了长期的抗瘤免疫记忆.
长期无瘤存活率显著改善.

结论:

PNBS/ diABZI是一种强大的增强STING免疫疗法的纳米激活剂.
通过系统间交叉来提高ROS生产的设计规则是有效的.
一类光敏化聚合物车辆有望克服STING免疫疗法耐药性.

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