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通过SORT脂质纳米颗粒共同传递向肺巨的RNAi和mRNA,增强了肺癌免疫疗法

Qing Liang¹, Yue Peng², Linyao Zhao³

¹Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

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

|December 10, 2025

概括

新的脂质纳米颗粒向SPP1+巨细胞,克服了非小细胞肺癌 (NSCLC) 新辅助免疫疗法的耐药性. 这种方法重编程巨细胞,增强抗瘤免疫力,并可能将不响应者转化为长期幸存者.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
纳米医学是一种纳米医学.

背景情况:

新辅助免疫疗法改善了可切除非小细胞肺癌 (NSCLC) 的术后治疗.
大约50%的患者对当前的免疫疗法没有反应.
已确定SPP1+巨细胞是NSCLC有效免疫疗法的关键障碍.

研究的目的:

开发一种针对NSCLC中SPP1+巨细胞的向输送系统.
为了研究SPP1-siRNA和干扰素-γ mRNA输送的协同效应.
为了增强抗瘤免疫力和克服免疫疗法耐药性.

主要方法:

工程修改的选择性器官向性脂质纳米颗粒 (SORT LNPs).
与SPP1-siRNA和干扰素-γ (IFN-γ) mRNA (siSPP1-mIFNγ@mLNPs) 一起加载的SORT LNP.
使用曼诺酶受体引导的输送用于肺部受限向SPP1+巨细胞.
在体内与免疫检查点抑制剂 (ICI) 结合使用时评估的疗效.

主要成果:

siSPP1-mIFNγ@mLNPs有效地将SPP1+巨细胞从M2类型重编程为瘤杀伤性表型.
联合交付证明了协同效应,超过了单个组件交付.
治疗显著提升了在正位肺癌和肺转移模型中的抗瘤免疫反应.
组合疗法将ICI无响应患者转化为长期生存者.

结论:

SPP1+巨细胞重编程是一种可行的策略,可以增强NSCLC免疫疗法.
修改了曼诺斯的SORT LNP为肺癌提供了精确的细胞类型向.
这种方法是一个有希望的策略,可以将免疫疗法不响应者转化为响应者.

关键词:

免疫治疗是一种免疫疗法.脂质纳米颗粒是一种纳米粒子.巨细胞是一个巨细胞.非小细胞肺癌是非小细胞肺癌.SPP1 SPP1 这是一个很好的选择.

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