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在固体瘤中,同时提供向CAF的纳米粒子,用于同时激活T细胞加NKT细胞攻击固体瘤

Yucheng Xiang¹, Lie Zhang², Jing Ye³

¹Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China; Sichuan Higher Education Institute Key Laboratory of Structure-Specific Small Molecule Drugs, Institute of Materia Medica, School of Pharmacy, Chengdu Medical College, Chengdu 610500, China.

Journal of advanced research

|March 10, 2026

概括

这项研究开发了一种能够分解瘤纤维化的纳米粒子,释放药物来激活免疫细胞并消除与癌症相关的纤维细胞. 这种方法在临床前模型中导致了显著的瘤根除和减少转移.

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:

瘤纤维化会形成一个物理障碍,通过限制免疫细胞透来阻碍免疫疗法.
克服这种免疫抑制障碍对于有效的癌症治疗至关重要.

研究的目的:

开发一个纤维细胞激活蛋白-α (FAP-α) 响应的纳米粒子输送系统, (α-GC/NAV) -CPC.
封装纳维托克拉克斯 (NAV) 和α-galactosylceramide (α-GC) 以在瘤微环境中向药物释放.

主要方法:

设计的两类块聚合物与FAP-α可降解链接器用于纳米粒子自组装.
同封装NAV和α-GC成为FAP-α响应的纳米粒子.
在三阴性乳腺癌模型中验证了纳米粒子疗效.

主要成果:

(α-GC/NAV) -CPC系统有效地拆除了FAP-α-阳性纤维细胞屏障,将瘤间歇性液压降低了4.9倍.
在瘤透NKT细胞 (超过5倍) 和T细胞 (超过4倍) 中取得显著增加.
具有强大的抗瘤活性,体内瘤根除率为66.7%,肺转移率降低.

结论:

响应FAP-α的纳米粒子系统成功克服瘤纤维化并增强抗瘤免疫力.
这一策略提供了一种有希望的方法,通过向瘤微环境来改善癌症免疫疗法.

关键词:

阿尔法-银河系糖胺.与癌症相关的纤维细胞.免疫治疗是一种免疫疗法.在 NKT 细胞中.固体瘤是一个固体瘤.

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