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通过CaCO₃纳米颗粒进行增强的骨髓瘤免疫疗法:重塑瘤酸性和免疫微环境,用于光动力疗法

Yinghua Gao^1,2, Zhuoying Wang¹, Xinmeng Jin¹

¹Department of Orthopedics, Shanghai Bone Tumor Institution, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Street, Shanghai, 200080, China.

Advanced healthcare materials

|May 17, 2024

概括

这项研究开发了一种新的纳米系统,通过中和酸性瘤微环境和重新编程免疫抑制细胞来对抗骨髓瘤 (OS). 这种方法提高了免疫治疗的有效性,并促进了长期的抗瘤免疫力.

科学领域:

在瘤学瘤学.
纳米医学是一种纳米医学.
免疫治疗是一种免疫疗法.

背景情况:

骨肉瘤 (OS) 的特点是"冷"的瘤微环境 (TME) 与M2表型瘤相关的巨细胞 (TAMs),阻碍免疫疗法的有效性.
由H+离子和乳酸酸驱动的酸性TME促进免疫抑制细胞,创造一种抑制瘤免疫微环境 (TIME).

研究的目的:

开发一个多目标协同组合策略,以中和酸性TME并重新编程TAM,以改善OS治疗.
评估一种基于碳酸/多多巴胺的新型纳米系统 (A-NPs@(SHK+Ce6) 与PD-1阻断相结合的疗效.

主要方法:

基于碳酸 (CaCO3) /多多巴胺 (PDA) 的纳米系统的开发 (A-NPs@(SHK+Ce6)).
使用CaCO3纳米颗粒来中和H+离子和加载的SHK来抑制乳酸生产,并与光动力学治疗 (PDT) 协同作用.
使用A-NPs@(SHK+Ce6) 和编程细胞死亡蛋白1 (PD-1) 检查点阻塞的组合疗法.

主要成果:

该纳米系统中和了酸性TME,逆转了TAM极化,并增强了PDT诱导的瘤抑制.
组合疗法显著消除了远处的瘤.
治疗促进了长期的免疫记忆,防止瘤复发.

结论:

一个新的多目标纳米系统通过共同调节酸性TME和TAM两极分化,有效地重编程TIME.
这一战略有望增强骨髓瘤免疫疗法,并建立持久的抗瘤免疫力.

关键词:

在PDT中使用PDT.这就是TAMs.酸性瘤微环境的微环境纳米系统纳米系统瘤免疫微环境是一个微环境.

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