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载有CXCR4抗剂的纳米粒子重编程瘤微环境,并增强肝细胞癌的免疫疗法

Sheng-Liang Cheng¹, Chien-Huang Wu², Yun-Jen Tsai³

¹Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan; International Intercollegiate PhD Program, National Tsing Hua University, Hsinchu 30013, Taiwan.

Journal of controlled release : official journal of the Controlled Release Society

|January 25, 2025

概括

研究人员开发了新型纳米粒子 (807-NPs),可以提供CXCR4对手来重新编程瘤微环境. 这种方法通过减少免疫抑制和促进抗瘤免疫反应,提高了肝细胞癌 (HCC) 的免疫疗法疗效.

科学领域:

在瘤学瘤学.
纳米技术纳米技术
免疫治疗是一种免疫疗法.

背景情况:

肝细胞癌 (HCC) 对晚期的治疗选择有限.
免疫抑制性瘤微环境 (TME) 阻碍了PD-1抑制剂在HCC中的有效性.
低氧驱动的CXCL12/CXCR4轴激活有助于免疫抑制的TME.

研究的目的:

开发和评估807-NPs,一种新型纳米粒子配方封装CXCR4抗剂 (BPRCX807),用于向HCC.
评估807-NP克服免疫抑制TME和增强癌症免疫疗法的能力.

主要方法:

开发脂涂层的酸纳米粒子 (807-NP) 封装BPRCX807.7.
在临床前模型中评估807-NP的药理动力学,瘤可用性和全身毒性.
评估807-NPs对HCC细胞,M2巨细胞和TME在 орто托普性小鼠HCC模型中的影响.
调查807-NPs对T细胞激活的影响及其与PD-1封锁和癌症疫苗的协同作用.

主要成果:

807-NP显示了BPRCX807的改善药理动力学和瘤输送,没有系统性毒性.
807-NP有效地阻断了CXCR4/CXCL12通路,抑制了Akt和mTOR信号传递.
观察到M2巨细胞重新偏向M1表型,并增加了细胞毒性T细胞透.
807-NPs的全身管理抑制了瘤生长和转移,并增强了免疫治疗的疗效.

结论:

基于纳米技术的CXCR4抗剂的输送具有癌症免疫治疗的巨大潜力.
807-NP可以重塑免疫抑制性TME,使HCC对现有疗法的反应更好.
这种方法提供了一个有前途的策略,以改善高级HCC的治疗结果.

关键词:

在CXCL12/CXCR4轴上肝细胞癌是肝细胞癌.免疫治疗是一种免疫疗法.这是一种PD-1抑制剂.与瘤相关的巨细胞.

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