通过协同性血栓形成和低氧激活化疗进行增强免疫治疗的血管向纳米平台
Pengfei Yuan1, Tianci Zhu1, Xiaodie Yan1
1Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Engineering Technology Research Center of Drug Carrier of Guangdong, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
ACS applied materials & interfaces
|May 30, 2025
概括
一个新的纳米平台结合了血栓形成和化疗,以增强癌症免疫疗法. 这种方法破坏了瘤的血液流动,激活了化疗,并刺激了针对癌症的强有力的免疫反应.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 癌症治疗 癌症治疗
背景情况:
- 瘤血管系统对于癌症的进展至关重要.
- 针对血管的疗法提供了有前途的治疗策略.
- 需要协同方法来克服治疗耐药性.
研究的目的:
- 开发一种针对血管的纳米平台 (ThT@ZRR) 用于协同的癌症治疗.
- 为了将血栓因子诱导的血栓形成与低氧激活化疗相结合.
- 增强抗瘤免疫力,克服免疫抵抗力.
主要方法:
- 开发ZIF-8纳米颗粒载有血栓素和提拉巴胺 (TPZ),覆盖着RGD修饰的红细胞膜.
- 释放响应pH的血栓,诱导局部血栓形成和缺氧.
- 低氧增强TPZ激活用于直接杀死瘤细胞和免疫细胞死亡 (ICD).
- 评估免疫反应,包括树突细胞成熟,T细胞透和巨细胞两极分化.
- 在小鼠黑色素瘤和三阴性乳腺癌模型中评估抗瘤疗效.
主要成果:
- ThT@ZRR纳米平台成功诱导局部血栓形成和恶化的瘤缺氧.
- 缺氧增强TPZ激活,导致瘤细胞死亡的增加.
- 治疗引发了强大的免疫反应,包括增强的CD8+T细胞透和促炎性巨细胞两极分化.
- 在黑色素瘤和三阴性乳腺癌模型中,ThT@ZRR显示出强大的抗瘤功效.
- 该纳米平台显示了适应不同瘤血管架构的适应性.
结论:
- 开发的纳米平台有效地结合了血管栓塞,缺氧激活化疗和免疫激活.
- 这种协同方法增强了抗瘤免疫力,克服了固体瘤中的免疫抵抗力.
- ThT@ZRR代表了改善癌症免疫治疗的有希望的策略.
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