Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Neurosurgery, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, MA 02129, USA; Harvard Medical School, Boston, MA 02115, USA.
J Control Release. 2023 Apr;356:493-506. doi: 10.1016/j.jconrel.2023.03.009. Epub 2023 Mar 15.
Diseases of the central nervous system (CNS) are challenging to treat, mainly due to the blood-brain barrier (BBB), which restricts drugs in circulation from entering target regions in the brain. To address this issue extracellular vesicles (EVs) have gained increasing scientific interest as carriers able to cross the BBB with multiplex cargos. EVs are secreted by virtually every cell, and their escorted biomolecules are part of an intercellular information gateway between cells within the brain and with other organs. Scientists have undertaken efforts to safeguard the inherent features of EVs as therapeutic delivery vehicles, such as protecting and transferring functional cargo, as well as loading them with therapeutic small molecules, proteins, and oligonucleotides and targeting them to specific cell types for the treatment of CNS diseases. Here, we review current emerging approaches that engineer the EV surface and cargo to improve targeting and functional responses in the brain. We summarize existing applications of engineered EVs as a therapeutic delivery platform for brain diseases, some of which have been evaluated clinically.
中枢神经系统(CNS)疾病的治疗具有挑战性,主要是由于血脑屏障(BBB)的存在,这限制了循环中的药物进入大脑中的靶区。为了解决这个问题,细胞外囊泡(EVs)作为能够携带多种货物穿越 BBB 的载体,引起了越来越多的科学兴趣。EVs 几乎是由每一个细胞分泌的,其携带的生物分子是大脑内细胞之间以及与其他器官之间细胞间信息传递的一个组成部分。科学家们已经努力保护 EVs 作为治疗性药物载体的固有特性,例如保护和传递功能货物,以及将它们装载到治疗性小分子、蛋白质和寡核苷酸中,并将它们靶向特定的细胞类型,以治疗 CNS 疾病。在这里,我们综述了当前新兴的工程化 EV 表面和货物的方法,以改善在大脑中的靶向和功能反应。我们总结了工程化 EV 作为治疗脑疾病的药物递送平台的现有应用,其中一些已经在临床上进行了评估。
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