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通过微波辐射获得的肿瘤衍生微粒可诱导肺腺癌发生免疫原性细胞死亡。

Tumour-derived microparticles obtained through microwave irradiation induce immunogenic cell death in lung adenocarcinoma.

作者信息

Wu Yali, Chen Wenjuan, Deng Jingjing, Cao Xinghui, Yang Zimo, Chen Jiangbin, Tan Qi, Zhou E, Li Minglei, Liu Jiatong, Guo Mengfei, Jin Yang

机构信息

Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hubei Province Key Laboratory of Biological Targeted Therapy, MOE Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Nat Nanotechnol. 2025 May 19. doi: 10.1038/s41565-025-01922-3.

DOI:10.1038/s41565-025-01922-3
PMID:40389640
Abstract

Tumour-derived microparticles (TMPs), extracellular vesicles traditionally obtained upon ultraviolet (UV) radiation of tumour cells, hold promise in tumour immunotherapies and vaccines and have demonstrated potential as drug delivery systems for tumour treatment. However, concerns remain regarding the limited efficacy and safety of UV-derived TMPs. Here we introduce a microwave (MW)-assisted method for preparing TMPs, termed MW-TMPs. Brief exposure of tumour cells to short-wavelength MW radiation promotes the release of TMPs showing superior in vivo antitumour activity and safety compared with UV-TMPs. MW-TMPs induce immunogenic cell death and reprogramme suppressive tumour immune microenvironments in different lung tumour models, enabling dual targeting of tumour cells by natural killer and T cells. We show that they can efficiently deliver methotrexate to tumours, synergistically boosting the efficacy of PD-L1 blockade. This MW-TMP development strategy is simpler, more efficient and safer than traditional UV-TMP methods.

摘要

肿瘤衍生的微粒(TMPs)是传统上通过对肿瘤细胞进行紫外线(UV)辐射而获得的细胞外囊泡,在肿瘤免疫疗法和疫苗方面具有前景,并已证明有潜力作为肿瘤治疗的药物递送系统。然而,对于紫外线衍生的TMPs的有限疗效和安全性仍存在担忧。在此,我们介绍一种用于制备TMPs的微波(MW)辅助方法,称为MW-TMPs。将肿瘤细胞短暂暴露于短波长MW辐射下可促进TMPs的释放,与UV-TMPs相比,MW-TMPs在体内显示出卓越的抗肿瘤活性和安全性。在不同的肺肿瘤模型中,MW-TMPs诱导免疫原性细胞死亡并重新编程抑制性肿瘤免疫微环境,使自然杀伤细胞和T细胞能够双重靶向肿瘤细胞。我们表明,它们可以有效地将甲氨蝶呤递送至肿瘤,协同增强PD-L1阻断的疗效。这种MW-TMP的开发策略比传统的UV-TMP方法更简单、更高效且更安全。

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本文引用的文献

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Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.细胞外囊泡研究的最低信息要求(MISEV2023):从基础到先进方法。
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IL-1β macrophages fuel pathogenic inflammation in pancreatic cancer.IL-1β 巨噬细胞促进胰腺癌发病炎症。
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Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis.
奶源性细胞外囊泡保护肠道-肝脏轴中肠道屏障的完整性。
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Cell death, therapeutics, and the immune response in cancer.细胞死亡、治疗学与癌症中的免疫反应。
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Copper-cysteamine nanoparticle-mediated microwave dynamic therapy improves cancer treatment with induction of ferroptosis.铜-半胱胺纳米颗粒介导的微波动态疗法通过诱导铁死亡改善癌症治疗。
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Tumor-derived extracellular vesicles in the colorectal cancer immune environment and immunotherapy.肿瘤来源的细胞外囊泡在结直肠癌免疫微环境和免疫治疗中的作用
Pharmacol Ther. 2023 Jan;241:108332. doi: 10.1016/j.pharmthera.2022.108332. Epub 2022 Dec 14.
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NK cells and solid tumors: therapeutic potential and persisting obstacles.自然杀伤细胞与实体瘤:治疗潜力与持续存在的障碍。
Mol Cancer. 2022 Nov 1;21(1):206. doi: 10.1186/s12943-022-01672-z.
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Extracellular-Vesicle-Based Drug Delivery Systems for Enhanced Antitumor Therapies through Modulating the Cancer-Immunity Cycle.基于细胞外囊泡的药物传递系统通过调节肿瘤免疫循环增强抗肿瘤治疗。
Adv Mater. 2022 Dec;34(52):e2201054. doi: 10.1002/adma.202201054. Epub 2022 Oct 13.
10
Phenotype Identification of HeLa Cells Knockout CDK6 Gene Based on Label-Free Raman Imaging.基于无标记拉曼成像的 HeLa 细胞 CDK6 基因敲除表型鉴定。
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