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可生物降解的聚合体封装过氧化铜和凝素用于向化疗免疫疗法

Man Lung Lee¹, Weiwei Jiang², Jack Chun Hin Chen³

¹Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, China.

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

|March 4, 2026

概括

这项研究引入了结合化疗和免疫疗法的新型纳米粒子,用于治疗三阴性乳腺癌. 这些纳米颗粒通过产生活性氧物种 (ROS) 来增强抗PD-L1免疫疗法来提高治疗效率.

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:

三重阴性乳腺癌 (TNBC) 对传统疗法表现出耐药性.
开发有针对性的药物输送系统对于有效的癌症治疗至关重要.
免疫疗法看起来很有前途,但在克服瘤微环境 (TME) 方面面临挑战.

研究的目的:

为向的TNBC治疗设计ROS响应的聚合体 (HA-PGC).
将化学动力学疗法与免疫疗法相结合,以增强抗癌效果.
通过将冷瘤转化为热瘤来克服TNBC的抵抗.

主要方法:

制造具有氨酸功能的聚合体 (HA-PGC) 封装着凝胺 (GEM) 和氧化铜纳米粒子 (CuO2).
在酸性TME中利用CuO2分解,通过芬顿式反应产生ROS.
评估ROS对凝胺激活,谷氨耗尽和免疫细胞死亡 (ICD) 的协同效应.
在TNBC模型中评估HA-PGC纳米粒子和抗PD-L1免疫疗法的联合疗效.

主要成果:

这种HA-PGC纳米粒子有效地向CD44过度表达的TNBC细胞.
诱导的ROS抑制了cytidine deaminase (CDA),增强了GEM激活,以及耗尽的谷氨 (GSH),减少了ROS的清理.
氧化应激促进了ICD,树突细胞成熟,并增加了瘤透的淋巴细胞.
纳米粒子平台将冷瘤转化为热瘤,显著提高了抗PD-L1免疫疗法的疗效.

结论:

展示了一种结合化学动力学治疗和免疫治疗的新型多功能纳米粒子平台.
这一策略显示出在三阴性乳腺癌治疗中克服耐药性的前景.
这些发现为设计智能免疫治疗系统提供了基础.

关键词:

化学动力学疗法是一种化学动力学疗法.寒冷的瘤是一个冷的瘤.免疫治疗是一种免疫疗法.金属过氧化物金属过氧化物

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