纳米颗粒 (NP) 介导的Siglec15沉默和巨细胞再极化,用于增强癌症免疫治疗
Xiaodi Liu1,2, Qi Zhang2,3, Yixia Liang3
1Department of Ultrasound, Laboratory of Ultrasound Imaging and Drug, West China Hospital, Sichuan University, Chengdu 610041, China.
Acta pharmaceutica Sinica. B
|December 4, 2023
概括
向的纳米颗粒将干扰素- (IFNγ) 和siRNA传递给与瘤相关的巨细胞,增强T细胞透和增殖,以改善癌症免疫治疗结果,特别是在肝细胞癌中.
科学领域:
- 免疫学 免疫学 免疫学
- 纳米技术 纳米技术
- 在瘤学瘤学.
背景情况:
- 对于癌症免疫疗法的成功,T细胞的透和增殖至关重要.
- 干扰素- (IFNγ) 促进T细胞的招募,而TAM中的Siglec15则抑制T细胞的增殖.
- 调节巨细胞功能提供了一种增强抗瘤免疫力的策略.
研究的目的:
- 开发用于IFNγ和Siglec15siRNA (siSiglec15) 的联合传递的降解反应纳米粒子.
- 通过同时促进T细胞透和增殖来增强癌症免疫疗法.
- 为了研究肝细胞癌 (HCC) 模型中的治疗潜力.
主要方法:
- 制造基于聚 (二硫化胺) 和脂质聚 (乙烯基醇) 的纳米粒子.
- 用siSiglec15和IFNγ.加载的纳米颗粒进行全身静脉注射.
- 评估纳米粒子积累,TAMs的细胞吸收,以及瘤组织中的载荷释放.
- 评估巨细胞再极化,T细胞反应和HCC瘤生长抑制.
主要成果:
- 纳米粒子有效地积聚在瘤组织中,并被TAMs内部化.
- 谷氨触发的IFNγ和siSiglec15再极化巨细胞的释放,增强T细胞的透和增殖.
- 联合治疗显著抑制了HCC瘤的生长,特别是免疫检查点抑制剂.
结论:
- 开发的纳米粒子有效地向TAM传递治疗有效载荷,以增强癌症免疫疗法.
- 该策略同时促进T细胞透和增殖,导致显著的瘤抑制.
- 这种方法代表了改善肝细胞癌治疗结果的有希望的工具.
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