工程化外泌体在肿瘤免疫研究中的应用。

Engineered exosomes for studies in tumor immunology.

机构信息

Georgia Cancer Center, Augusta University, Augusta, Georgia, USA.

Cedars-Sinai Medical Center, Los Angeles, California, USA.

出版信息

Immunol Rev. 2022 Nov;312(1):76-102. doi: 10.1111/imr.13107. Epub 2022 Jul 8.

Abstract

Exosomes are a type of extracellular vesicle (EV) with diameters of 30-150 nm secreted by most of the cells into the extracellular spaces and can alter the microenvironment through cell-to-cell interactions by fusion with the plasma membrane and subsequent endocytosis and release of the cargo. Because of their biocompatibility, low toxicity and immunogenicity, permeability (even through the blood-brain barrier (BBB)), stability in biological fluids, and ability to accumulate in the lesions with higher specificity, investigators have started making designer's exosomes or engineered exosomes to carry biologically active protein on the surface or inside the exosomes as well as using exosomes to carry drugs, micro RNA, and other products to the site of interest. In this review, we have discussed biogenesis, markers, and contents of various exosomes including exosomes of immune cells. We have also discussed the current methods of making engineered and designer's exosomes as well as the use of engineered exosomes targeting different immune cells in the tumors, stroke, as well as at peripheral blood. Genetic engineering and customizing exosomes create an unlimited opportunity to use in diagnosis and treatment. Very little use has been discovered, and we are far away to reach its limits.

摘要

外泌体是一种直径为 30-150nm 的细胞外囊泡(EV),大多数细胞都会分泌外泌体进入细胞外空间,并通过与质膜融合以及随后的内吞作用和货物释放,通过细胞间的相互作用改变微环境。由于其具有生物相容性、低毒性和免疫原性、通透性(甚至可穿过血脑屏障(BBB))、在生物体液中的稳定性以及在病变部位更高的特异性聚集能力,研究人员已开始制造设计的外泌体或工程化的外泌体,在表面或内部携带具有生物活性的蛋白质,以及利用外泌体将药物、micro RNA 和其他产品输送到靶部位。在这篇综述中,我们讨论了各种外泌体(包括免疫细胞的外泌体)的生物发生、标志物和内容。我们还讨论了目前制造工程化和设计的外泌体的方法,以及利用针对肿瘤、中风和外周血中不同免疫细胞的工程化外泌体的方法。遗传工程和定制外泌体为诊断和治疗提供了无限的机会。目前发现的应用非常有限,我们离达到其极限还很远。

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